Computational Bio-Engineering : Scipedia

A non-intrusive proper generalized decomposition scheme with application in biomechanics
X. Zou, M. Conti, P. Diez, F. Auricchio

Int. J. Numer. Meth. Engng. (2018). (Preprint) Vol. 113 (2), pp. 230-251

Abstract
Proper generalized decomposition (PGD) is often used for multi-query and fast-response simulations. It is a powerful tool alleviating the curse of dimensionality affecting multi-parametric partial differential equations. Most implementations of PGD are intrusive extensions based on in-house developed finite element (FE) solvers. In this work, we propose a non-intrusive PGD scheme using off-the-shelf FE codes (such as certified commercial software) as an external solver. The scheme is implemented and monitored by in-house flow-control codes. A typical implementation is provided with downloadable codes. Moreover, a novel parametric separation strategy for the PGD resolution is presented. The parametric space is split into two- or three-dimensional subspaces, to allow PGD technique solving problems with constrained parametric spaces, achieving higher convergence ratio. Numerical examples are provided. In particular, a practical example in biomechanics is included, with potential application to patient-specific simulation.
Abstract
Proper generalized decomposition (PGD) is often used for multi-query and fast-response simulations. It is a powerful tool alleviating the curse of dimensionality affecting [...]
- 21
- read
A reduced-order model based on the coupled 1D-3D finite element simulations for an efficient analysis of hemodynamics problems
E. Soudah, R. Rossi, S. Idelsohn, E. Oñate

Computational Mechanics (2014). Vol. 54 (4), pp. 1013-1022

Abstract
A reduced-order model for an efficient analysis of cardiovascular hemodynamics problems using multiscale approach is presented in this work. Starting from a patient-specific computational mesh obtained by medical imaging techniques, an analysis methodology based on a two-step automatic procedure is proposed. First a coupled 1D-3D Finite Element Simulation is performed and the results are used to adjust a reduced-order model of the 3D patient-specific area of interest. Then, this reduced-order model is coupled with the 1D model. In this way, three-dimensional effects are accounted for in the 1D model in a cost effective manner, allowing fast computation under different scenarios. The methodology proposed is validated using a patient-specific aortic coarctation model under rest and non-rest conditions.
Abstract
A reduced-order model for an efficient analysis of cardiovascular hemodynamics problems using multiscale approach is presented in this work. Starting from a patient-specific [...]
- 14
- read
Statistical analysis for rupture risk prediction of abdominal aortic aneurysms (AAA) based on its morphometry
G. Vilalta, J. Vilalta, E. Soudah, F. Nieto, L. Lipsa, M. Pérez, B. López, C. Vaquero

Journal of Mechanics in Medicine and Biology (2017). Vol. 17 (4), pp. 1-23

Abstract
The morphometry of the abdominal aortic aneurysms (AAA) it has been recognized as one of the main factors that may predispose its rupture. The variation of the AAA morphometry, over time, induces modifications in hemodynamic behavior which, in turn, alters the spatial and temporal distribution of hemodynamic stress on the aneurismatic wall, establishing a bidirectional process that can influence the rupture phenomenon. In order to evaluate potential correlations between the main geometric parameters characterizing the AAA and hemodynamic stresses, 13 unrupture AAA patient-specific models were created. To AAA geometric characterization, twelve indices based on lumen center line were defined and determined. The computing of temporal and spatial distributions of hemodynamic stresses was conducted through Computational Fluid Dynamics. Statistical techniques were used to assess the relationships between the hemodynamic parameters and the different geometrical indices of the AAA. Regression analyses were conducted to obtain linear predictor models for hemodynamic stresses using the different indices defined in this paper as predictor variables. The statistical analysis confirmed that the length L, the asymmetry and the saccular index significantly influenced the hemodynamic stresses. The results obtained show the potential of the use of statistical techniques in predicting the rupture risk of patient-specific AAA.
Abstract
The morphometry of the abdominal aortic aneurysms (AAA) it has been recognized as one of the main factors that may predispose its rupture. The variation of the AAA morphometry, [...]
- 9
- read
A general constitutive model for vascular tissue considering stress driven growth and biological availability
F. Bellomo, S. Oller, F. Armero, L. Nallim

Computer modeling in engineering and sciencies (2011). Vol. 80 (1), pp. 1-22

Abstract
Some of the key factors that regulate growth and remodeling of tissues are fundamentally mechanical. However, it is important to take into account the role of biological availability to generate new tissue together with the stresses and strains in the processes of natural or pathological growth. In this sense, the model presented in this work is oriented to describe growth of vascular tissue under "stress driven growth" considering biological availability of the organism. The general theoretical framework is given by a kinematic formulation in large strain combined with the thermodynamic basis of open systems. The formulation uses a multiplicative decomposition of deformation gradient, splitting it in a growth part and visco-elastic part. The strains due to growth are incompatible and are controlled by unbalanced stresses related to a homeostatic state. Growth implies a volume change with an increase of mass maintaining constant the density. One of the most interesting features of the proposed model is the generation of new tissue taking into account the contribution of mass to the system controlled through the biological availability. Because soft biological tissues in general have a hierarchical structure with several components (usually a soft matrix reinforced with collagen fibers), the developed growth model is suitable for the growth characterization of each component. This allows considering a different behavior for each of them in the context of a generalized theory of mixtures.
Abstract
Some of the key factors that regulate growth and remodeling of tissues are fundamentally mechanical. However, it is important to take into account the role of biological availability [...]
- 8
- read
Planar differential growth rates initiate precise fold positions in complex epithelia
M. Tozlouglu, M. Duda, N. Kirkland, R. Barrientos, J. Burden, J. Muñoz, Y. Mao

Developmental cell (2019). Vol. 51 (3), pp. 299-312

Abstract
Tissue folding is a fundamental process that shapes epithelia into complex 3D organs. The initial positioning of folds is the foundation for the emergence of correct tissue morphology. Mechanisms forming individual folds have been studied, but the precise positioning of folds in complex, multi-folded epithelia is less well-understood. We present a computational model of morphogenesis, encompassing local differential growth and tissue mechanics, to investigate tissue fold positioning. We use the Drosophila wing disc as our model system and show that there is spatial-temporal heterogeneity in its planar growth rates. This differential growth, especially at the early stages of development, is the main driver for fold positioning. Increased apical layer stiffness and confinement by the basement membrane drive fold formation but influence positioning to a lesser degree. The model successfully predicts the in vivo morphology of overgrowth clones and wingless mutants via perturbations solely on planar differential growth in silico.
Abstract
Tissue folding is a fundamental process that shapes epithelia into complex 3D organs. The initial positioning of folds is the foundation for the emergence of correct tissue [...]
- 8
- read
Coronal advanced flap in combination with a connective tissue graft. Is the thickness of the flap a predictor for root coverage? A prospective clinical study
T. Garces-McIntyre, J. Carbonell, L. Vallcorba, A. Santos, C. Valles, J. Nart

Journal of Clinical Periodontology (2017). Vol. 44 (9), pp. 933-940

Abstract
Aim Evaluate if there is any relationship between the flap thickness (FT) and the presence of complete root coverage (CRC) when performing coronally advanced flaps in combination with a connective tissue graft (CTG). Materials and methods Prospective clinical study, in which multiple Miller class I and II recessions were treated with a coronally advanced flap and a CTG standardized at 1 mm of thickness. Individual stents permitted repeated measurements of conventional periodontal parameters at the same point. The primary outcome variable was CRC. Secondary outcomes were recession reduction, gingival thickness and width of keratinized tissue (KT) achieved at 6 months post‐surgery. Results Forty‐five recessions (2.4 ± 0.75 mm) were treated in 20 patients. Mean root coverage was 93.4 ± 10.98%; 65% achieved CRC. The mean FT was 1.01 mm ± 0.64 mm and 1.01 ± 0.61 mm at 2 and 5 mm from the gingival margin, respectively. No relationship could be found between FT and CRC (p > .05). Statistical significant changes (p < .05) were observed for recession depth, clinical attachment level, KT and soft tissue thickness at the end of the study. Conclusions Flap thickness seems not to be a predictor for CRC when performing a coronally advanced flap plus a CTG. This technique may be of choice when treating thin biotypes.
Abstract
Aim Evaluate if there is any relationship between the flap thickness (FT) and the presence of complete root coverage (CRC) when performing coronally advanced flaps in [...]
- 7
- read
The plasma membrane as a mechanochemical transducer
A. Roux, X. Quiroga, N. Walani, M. Arroyo, P. Roca

Philosophical transaction of the Royal Society B. Diological sciences (2019). Vol. 374, pp. 1-15

Abstract
Cells are constantly submitted to external mechanical stresses, which they must withstand and respond to. By forming a physical boundary between cells and their environment that is also a biochemical platform, the plasma membrane (PM) is a key interface mediating both cellular response to mechanical stimuli, and subsequent biochemical responses. Here, we review the role of the PM as a mechanosensing structure. We first analyse how the PM responds to mechanical stresses, and then discuss how this mechanical response triggers downstream biochemical responses. The molecular players involved in PM mechanochemical transduction include sensors of membrane unfolding, membrane tension, membrane curvature or membrane domain rearrangement. These sensors trigger signalling cascades fundamental both in healthy scenarios and in diseases such as cancer, which cells harness to maintain integrity, keep or restore homeostasis and adapt to their external environment. This article is part of a discussion meeting issue ‘Forces in cancer: interdisciplinary approaches in tumour mechanobiology’.
Abstract
Cells are constantly submitted to external mechanical stresses, which they must withstand and respond to. By forming a physical boundary between cells and their environment [...]
- 6
- read
Hydraulic fracturing in cells and tissues: fracking meets cell biology
M. Arroyo, X. Trepat

Current opinion in cell biology (2017). Vol. 44, pp. 1-6 (Preprint)

Abstract
The animal body is largely made of water. A small fraction of body water is freely flowing in blood and lymph, but most of it is trapped in hydrogels such as the extracellular matrix (ECM), the cytoskeleton, and chromatin. Besides providing a medium for biological molecules to diffuse, water trapped in hydrogels plays a fundamental mechanical role. This role is well captured by the theory of poroelasticity, which explains how any deformation applied to a hydrogel causes pressure gradients and water flows, much like compressing a sponge squeezes water out of it. Here we review recent evidence that poroelastic pressures and flows can fracture essential biological barriers such as the nuclear envelope, the cellular cortex, and epithelial layers. This type of fracture is known in engineering literature as hydraulic fracturing or ‘fracking’.
Abstract
The animal body is largely made of water. A small fraction of body water is freely flowing in blood and lymph, but most of it is trapped in hydrogels such as the extracellular [...]
- 6
- read
Confined bilayers passively regulate shape and stress
M. Staykova, M. Arroyo, M. Rahimi, H. Stone

Physical review letters (2013). Vol. 110 (2), pp. 1-5 (Preprint)

Abstract
Lipid membranes are commonly confined to adjacent subcellular structures or to artificial substrates and particles. We develop an experimental and theoretical framework to investigate the mechanics of confined membranes, including the influence of adhesion, strain, and osmotic pressure. We find that supported lipid bilayers respond to stress by nucleating and evolving spherical and tubular protrusions. In cells, such transformations are generally attributed to proteins. Our results offer insights into the mechanics of cell membranes and can further extend the applications of supported bilayers.
Abstract
Lipid membranes are commonly confined to adjacent subcellular structures or to artificial substrates and particles. We develop an experimental and theoretical framework to [...]
- 5
- read
Active superelasticity in three-dimensional epithelia of controlled shape
E. Latorre, S. Kale, L. Casares, M. Gómez-González, M. Uroz, L. Valon, R. Nair, E. Garreta, N. Monstserrat, A. Campo, B. Ladoux, M. Arroyo, X. Trepat

Nature (2018). Vol. 563 (7730), pp. 203-208 (Preprint)

Abstract
Fundamental biological processes are carried out by curved epithelial sheets that enclose a pressurized lumen. How these sheets develop and withstand three-dimensional deformations has remained unclear. Here we combine measurements of epithelial tension and shape with theoretical modelling to show that epithelial sheets are active superelastic materials. We produce arrays of epithelial domes with controlled geometry. Quantification of luminal pressure and epithelial tension reveals a tensional plateau over several-fold areal strains. These extreme strains in the tissue are accommodated by highly heterogeneous strains at a cellular level, in seeming contradiction to the measured tensional uniformity. This phenomenon is reminiscent of superelasticity, a behaviour that is generally attributed to microscopic material instabilities in metal alloys. We show that in epithelial cells this instability is triggered by a stretch-induced dilution of the actin cortex, and is rescued by the intermediate filament network. Our study reveals a type of mechanical behaviour—which we term active superelasticity—that enables epithelial sheets to sustain extreme stretching under constant tension.
Abstract
Fundamental biological processes are carried out by curved epithelial sheets that enclose a pressurized lumen. How these sheets develop and withstand three-dimensional deformations [...]
- 5
- read
Estimation of wall shear stress using 4D flow cardiovascular MRI and computational fluid dynamics
E. Soudah, J. Casacuberta, P. Gámez-Montero, G. Raush, R. Castilla

Journal of Mechanics in Medicine and Biology (2016). Vol. 17 (3), pp. 1-16 (Preprint)

Abstract
Company In the last few years, wall shear stress (WSS) has arisen as a new diagnostic indicator in patients with arterial disease. There is a substantial evidence that the WSS plays a significant role, together with hemodynamic indicators, in initiation and progression of the vascular diseases. Estimation of WSS values, therefore, may be of clinical significance and the methods employed for its measurement are crucial for clinical community. Recently, four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has been widely used in a number of applications for visualization and quantification of blood flow, and although the sensitivity to blood flow measurement has increased, it is not yet able to provide an accurate three-dimensional (3D) WSS distribution. The aim of this work is to evaluate the aortic blood flow features and the associated WSS by the combination of 4D flow cardiovascular magnetic resonance (4D CMR) and computational fluid dynamics technique. In particular, in this work, we used the 4D CMR to obtain the spatial domain and the boundary conditions needed to estimate the WSS within the entire thoracic aorta using computational fluid dynamics. Similar WSS distributions were found for cases simulated. A sensitivity analysis was done to check the accuracy of the method. 4D CMR begins to be a reliable tool to estimate the WSS within the entire thoracic aorta using computational fluid dynamics. The combination of both techniques may provide the ideal tool to help tackle these and other problems related to wall shear estimation
Abstract
Company In the last few years, wall shear stress (WSS) has arisen as a new diagnostic indicator in patients with arterial disease. There is a substantial evidence that the [...]
- 5
- read
Analysis of uncertainty and variability in finite element computational models for biomedical engineering: characterization and propagation
N. Mangado, G. Piella, J. Noailly, J. Pons Prats, M. Ballester

Frontiers in Bioengineering and Biotechnology (2016). Vol. 4, pp. 1-17

Abstract
Computational modeling has become a powerful tool in biomedical engineering thanks to its potential to simulate coupled systems. However, real parameters are usually not accurately known, and variability is inherent in living organisms. To cope with this, probabilistic tools, statistical analysis and stochastic approaches have been used. This article aims to review the analysis of uncertainty and variability in the context of finite element modeling in biomedical engineering. Characterization techniques and propagation methods are presented, as well as examples of their applications in biomedical finite element simulations. Uncertainty propagation methods, both non-intrusive and intrusive, are described. Finally, pros and cons of the different approaches and their use in the scientific community are presented. This leads us to identify future directions for research and methodological development of uncertainty modeling in biomedical engineering.
Abstract
Computational modeling has become a powerful tool in biomedical engineering thanks to its potential to simulate coupled systems. However, real parameters are usually not accurately [...]
- 4
- read
Shape control of active surfaces inspired by the movement of euglenids
M. Arroyo, A. DeSimone

Journal of the Mechanics and Physics of Solids (2014). Vol. 62, pp. 99-112 (Preprint)

Abstract
We examine a novel mechanism for active surface morphing inspired by the cell body deformations of euglenids. Actuation is accomplished through in-plane simple shear along prescribed slip lines decorating the surface. Under general non-uniform actuation, such local deformation produces Gaussian curvature, and therefore leads to shape changes. Geometrically, a deformation that realizes the prescribed local shear is an isometric embedding. We explore the possibilities and limitations of this bio- inspired shape morphing mechanism, by first characterizing isometric embeddings un- der axisymmetry, understanding the limits of embeddability, and studying in detail the accessibility of surfaces of zero and constant curvature. Modeling mechanically the active surface as a non-Euclidean plate (NEP), we further examine the mechanism beyond the geometric singularities arising from embeddability, where mechanics and buckling play a decisive role. We also propose a non-axisymmetric actuation strategy to accomplish large amplitude bending and twisting motions of elongated cylindrical surfaces. Besides helping understand how euglenids delicately control their shape, our results may provide the background to engineer soft machines
Abstract
We examine a novel mechanism for active surface morphing inspired by the cell body deformations of euglenids. Actuation is accomplished through in-plane simple shear along [...]
- 4
- read
Relaxation dynamics of fluid membranes
M. Arroyo, A. DeSimone

Physical review E: statistical, nonlinear and soft matter physics (2009). Vol. 79 (3), pp. 031915-1/031915-17

Abstract
We study the effect of membrane viscosity in the dynamics of liquid membranes{possibly with free or internal boundaries{ driven by conservative forces (curvature elasticity and line tension) and dragged by the bulk dissipation of the ambient fluid and the friction occurring when the amphiphilic molecules move relative to each other. To this end, we formulate a continuum model which includes a new form of the governing equations for a two-dimensional viscous fluid moving on a curved, time-evolving surface. The effect of membrane viscosity has received very limited attention in previous continuum studies of the dynamics of fluid membranes, although recent coarse-grained discrete simulations suggest its importance. By applying our model to the study of vesiculation and membrane fusion in a simpli ed geometry, we conclude that membrane viscosity plays a dominant role in the relaxation dynamics of fluid membranes of sizes comparable to those found in eukaryotic cells, and is not negligible in many large synthetic systems of current interest.
Abstract
We study the effect of membrane viscosity in the dynamics of liquid membranes{possibly with free or internal boundaries{ driven by conservative forces (curvature elasticity [...]
- 4
- read
Physical principles of membrane remodelling during cell mechanoadaptation
A. Kosmalska, L. Casares, A. Elosegui-Artola, J. Thottacherry, R. Moreno-Vicente, V. González-Tarragó, M. Pozo, S. Mayor, M. Arroyo, D. Navajas, X. Trepat, N. Gauthier, P. Roca

Nature communications (2015). Vol. 6 (7292), pp. 1-11

Abstract
Biological processes in any physiological environment involve changes in cell shape, which must be accommodated by their physical envelope-the bilayer membrane. However, the fundamental biophysical principles by which the cell membrane allows for and responds to shape changes remain unclear. Here we show that the 3D remodelling of the membrane in response to a broad diversity of physiological perturbations can be explained by a purely mechanical process. This process is passive, local, almost instantaneous, before any active remodelling and generates different types of membrane invaginations that can repeatedly store and release large fractions of the cell membrane. We further demonstrate that the shape of those invaginations is determined by the minimum elastic and adhesive energy required to store both membrane area and liquid volume at the cell-substrate interface. Once formed, cells reabsorb the invaginations through an active process with duration of the order of minutes.
Abstract
Biological processes in any physiological environment involve changes in cell shape, which must be accommodated by their physical envelope-the bilayer membrane. However, the [...]
- 4
- read
Mechanical stress in abdominal aortic aneurysms using artificial neural networks
E. Soudah, J. Rodríguez, R. López

Journal of Mechanics in Medicine and Biology (2015). Vol. 15 (3), p. 1550029

Abstract
Combination of numerical modeling and artificial intelligence (AI) in bioengineering processes are a promising pathway for the further development of bioengineering sciences. The objective of this work is to use Artificial Neural Networks (ANN) to reduce the long computational times needed in the analysis of shear stress in the Abdominal Aortic Aneurysm (AAA) by finite element methods (FEM). For that purpose two different neural networks are created. The first neural network (Mesh Neural Network, MNN) creates the aneurysm geometry in terms of four geometrical factors (asymmetry factor, aneurism diameter, aneurism thickness, aneurism length). The second neural network (Tension Neural Network, TNN) combines the results of the first neural network with the arterial pressure (new factor) to obtain the maximum stress distribution (output variable) in the aneurysm wall. The use of FEM for the analysis and design of bioengineering processes often requires high computational costs, but if this technique is combined with artificial intelligence, such as neural networks, the simulation time is significantly reduced. The shear stress obtained by the artificial neural models developed in this work achieved 95% of accuracy respect to the wall stress obtained by the FEM. On the other hand, the computational time is significantly reduced compared to the FEM.
Abstract
Combination of numerical modeling and artificial intelligence (AI) in bioengineering processes are a promising pathway for the further development of bioengineering [...]
- 4
- read
Development and validation of a multivariate predictive model for rheumatoid arthritis mortality using a machine learning approach
J. Lezcano-Valverde, F. Salazar, L. León, E. Toledano, J. Jover, B. Fernandez-Gutierrez, E. Soudah, I. González-Álvaro, L. Abasolo, L. Rodríguez-Rodríguez

Scientific Reports (2017). Vol. 7 (1), p. 10189

Abstract
We developed and independently validated a rheumatoid arthritis (RA) mortality prediction model using the machine learning method Random Survival Forests (RSF). Two independent cohorts from Madrid (Spain) were used: the Hospital Clínico San Carlos RA Cohort (HCSC-RAC; training; 1,461 patients), and the Hospital Universitario de La Princesa Early Arthritis Register Longitudinal study (PEARL; validation; 280 patients). Demographic and clinical-related variables collected during the first two years after disease diagnosis were used. 148 and 21 patients from HCSC-RAC and PEARL died during a median follow-up time of 4.3 and 5.0 years, respectively. Age at diagnosis, median erythrocyte sedimentation rate, and number of hospital admissions showed the higher predictive capacity. Prediction errors in the training and validation cohorts were 0.187 and 0.233, respectively. A survival tree identified five mortality risk groups using the predicted ensemble mortality. After 1 and 7 years of follow-up, time-dependent specificity and sensitivity in the validation cohort were 0.79–0.80 and 0.43–0.48, respectively, using the cut-off value dividing the two lower risk categories. Calibration curves showed overestimation of the mortality risk in the validation cohort. In conclusion, we were able to develop a clinical prediction model for RA mortality using RSF, providing evidence for further work on external validation.
Abstract
We developed and independently validated a rheumatoid arthritis (RA) mortality prediction model using the machine learning method Random Survival Forests (RSF). Two [...]
- 4
- read
Collective cell durotaxis emerges from long-range intercellular force transmission
R. Sunyer, V. Conte, J. Escribano, A. Elosegui-Artola, A. Labernadie, L. Valon, D. Navajas, J. García-Aznar, J. Muñoz, P. Roca-Cusachs, X. Trepat

Science (2016). Vol. 353 (6304), pp. 1157-1161 (Preprint)

Abstract
The ability of cells to follow gradients of extracellular matrix stiffness—durotaxis—has been implicated in development, fibrosis, and cancer. Here, we found multicellular clusters that exhibited durotaxis even if isolated constituent cells did not. This emergent mode of directed collective cell migration applied to a variety of epithelial cell types, required the action of myosin motors, and originated from supracellular transmission of contractile physical forces. To explain the observed phenomenology, we developed a generalized clutch model in which local stick-slip dynamics of cell-matrix adhesions was integrated to the tissue level through cell-cell junctions. Collective durotaxis is far more efficient than single-cell durotaxis; it thus emerges as a robust mechanism to direct cell migration during development, wound healing, and collective cancer cell invasion.
Abstract
The ability of cells to follow gradients of extracellular matrix stiffness—durotaxis—has been implicated in development, fibrosis, and cancer. Here, we found multicellular [...]
- 4
- read
Physiology-based model of cell viscoelasticity
J. Muñoz, S. Albo

Physical review E: statistical, nonlinear and soft matter physics (2013). Vol. 88 (1), pp. 1-8 (Preprint)

Abstract
The measured viscoelastic properties of biological tissues is the result of the passive and active response of the cells. We propose an evolution law of the remodeling process in the cytoskeleton which is able to mimic the viscous properties of biological cellular tissues. Our model is based on dynamical changes of the resting length. We show that under the small strain regime, the linear rheology models are recovered, with the relaxation time being replaced by the cell resistance to remodel. We implement the one-dimensional model into network systems of two and three dimensions, and show that the same conclusions may be drawn for those systems.
Abstract
The measured viscoelastic properties of biological tissues is the result of the passive and active response of the cells. We propose an evolution law of the remodeling process [...]
- 4
- read
An adaptive meshfree method for phase-field models of biomembranes. Part I: Approximation with maximum-entropy basis functions
A. Rosolen, C. Peco, M. Arroyo

Journal of Computational Physics (2013). Vol. 249 (15), pp. 303-319 (Preprint)

Abstract
We present an adaptive meshfree method to approximate phase-field models of biomembranes. In such models, the Helfrich curvature elastic energy, the surface area, and the enclosed volume of a vesicle are written as functionals of a continuous phase-field, which describes the interface in a smeared manner. Such functionals involve up to second-order spatial derivatives of the phase-field, leading to fourth-order Euler–Lagrange partial differential equations (PDE). The solutions develop sharp internal layers in the vicinity of the putative interface, and are nearly constant elsewhere. Thanks to the smoothness of the local maximum-entropy (max-ent) meshfree basis functions, we approximate numerically this high-order phase-field model with a direct Ritz–Galerkin method. The flexibility of the meshfree method allows us to easily adapt the grid to resolve the sharp features of the solutions. Thus, the proposed approach is more efficient than common tensor product methods (e.g. finite differences or spectral methods), and simpler than unstructured Cº finite element methods, applicable by reformulating the model as a system of second-order PDE. The proposed method, implemented here under the assumption of axisymmetry, allows us to show numerical evidence of convergence of the phase-field solutions to the sharp interface limit as the regularization parameter approaches zero. In a companion paper, we present a Lagrangian method based on the approximants analyzed here to study the dynamics of vesicles embedded in a viscous fluid. We present an adaptive meshfree method to approximate phase-field models of biomembranes. In such models, the Helfrich curvature elastic energy, the surface area, and the enclosed volume of a vesicle are written as functionals of a continuous phase-field, which describes the interface in a smeared manner. Such functionals involve up to second-order spatial derivatives of the phase-field, leading to fourth-order Euler–Lagrange partial differential equations (PDE). The solutions develop sharp internal layers in the vicinity of the putative interface, and are nearly constant elsewhere. Thanks to the smoothness of the local maximum-entropy (max-ent) meshfree basis functions, we approximate numerically this high-order phase-field model with a direct Ritz–Galerkin method. The flexibility of the meshfree method allows us to easily adapt the grid to resolve the sharp features of the solutions. Thus, the proposed approach is more efficient than common tensor product methods (e.g. finite differences or spectral methods), and simpler than unstructured C0C0 finite element methods, applicable by reformulating the model as a system of second-order PDE. The proposed method, implemented here under the assumption of axisymmetry, allows us to show numerical evidence of convergence of the phase-field solutions to the sharp interface limit as the regularization parameter approaches zero. In a companion paper, we present a Lagrangian method based on the approximants analyzed here to study the dynamics of vesicles embedded in a viscous fluid.
Abstract
We present an adaptive meshfree method to approximate phase-field models of biomembranes. In such models, the Helfrich curvature elastic energy, the surface area, and the [...]
- 3
- read
Shape transformations of lipid bilayers following rapid cholesterol uptake
M. Rahimi, D. Regan, M. Arroyo, A. Subramaniam, H. Stone, M. Staykova

Biophysical journal (2016). Vol. 111 (12), pp. 2651-2657 (Preprint)

Abstract
High cholesterol levels in the blood increase the risk of atherosclerosis. A common explanation is that the cholesterol increase in the plasma membrane perturbs the shape and functions of cells by disrupting the cell signaling pathways and the formation of membrane rafts. In this work, we show that after enhanced transient uptake of cholesterol, mono-component lipid bilayers change their shape similarly to cell membranes in vivo. The bilayers either expel lipid protrusions or spread laterally as a result of the ensuing changes in their lipid density, the mechanical constraints imposed on them, and the properties of cyclodextrin used as a cholesterol donor. In light of the increasingly recognized link between membrane tension and cell behavior, we propose that the physical adaptation of the plasma membrane to cholesterol uptake may play a substantial role in the biological response.
Abstract
High cholesterol levels in the blood increase the risk of atherosclerosis. A common explanation is that the cholesterol increase in the plasma membrane perturbs the shape [...]
- 3
- read
An adaptive meshfree method for phase-field models of biomembranes. Part II: A Lagrangian approach for membranes in viscous fluids
C. Peco, A. Rosolen, M. Arroyo

Journal of Computational Physics (2013). Vol. 249 (5), pp. 320-336 (Preprint)

Abstract
We present a Lagrangian phase-field method to study the low Reynolds number dynamics of vesicles embedded in a viscous fluid. In contrast to previous approaches, where the field variables are the phase-field and the fluid velocity, here we exploit the fact that the phasefield tracks a material interface to reformulate the problem in terms of the Lagrangian motion of a background medium, containing both the biomembrane and the fluid. We discretize the equations in space with maximum-entropy approximants, carefully shown to perform well in phase-field models of biomembranes in a companion paper. The proposed formulation is variational, lending itself to implicit time-stepping algorithms based on minimization of a time-incremental energy, which are automatically nonlinearly stable. The proposed method deals with two of the major challenges in the numerical treatment of coupled fluid/phase-field models of biomembranes, namely the adaptivity of the grid to resolve the sharp features of the phase-field, and the stiffness of the equations, leading to very small time-steps. In our method, local refinement follows the features of the phasefield as both are advected by the Lagrangian motion, and large time-steps can be robustly chosen in the variational time-stepping algorithm, which also lends itself to time adaptivity. The method is presented in the axisymmetric setting, but it can be directly extended to 3D. We present a Lagrangian phase-field method to study the low Reynolds number dynamics of vesicles embedded in a viscous fluid. In contrast to previous approaches, where the field variables are the phase-field and the fluid velocity, here we exploit the fact that the phase-field tracks a material interface to reformulate the problem in terms of the Lagrangian motion of a background medium, containing both the biomembrane and the fluid. We discretize the equations in space with maximum-entropy approximants, carefully shown to perform well in phase-field models of biomembranes in a companion paper. The proposed formulation is variational, lending itself to implicit time-stepping algorithms based on minimization of a time-incremental energy, which are automatically nonlinearly stable. The proposed method deals with two of the major challenges in the numerical treatment of coupled fluid/phase-field models of biomembranes, namely the adaptivity of the grid to resolve the sharp features of the phase-field, and the stiffness of the equations, leading to very small time-steps. In our method, local refinement follows the features of the phase-field as both are advected by the Lagrangian motion, and large time-steps can be robustly chosen in the variational time-stepping algorithm, which also lends itself to time adaptivity. The method is presented in the axisymmetric setting, but it can be directly extended to 3D.
Abstract
We present a Lagrangian phase-field method to study the low Reynolds number dynamics of vesicles embedded in a viscous fluid. In contrast to previous approaches, where the [...]
- 3
- read
Approximation of tensor fields on surfaces of arbitrary topology based on local Monge parametrizations
A. Torres-Sánchez, D. Santos-Oliván, M. Arroyo

Journal of Computational Physics (2020). Vol. 405, pp. 109168

Abstract
We introduce a new method, the Local Monge Parametrizations (LMP) method, to approximate tensor fields on general surfaces given by a collection of local parametrizations, e.g. as in finite element or NURBS surface representations. Our goal is to use this method to solve numerically tensor-valued partial differential equations (PDEs) on surfaces. Previous methods use scalar potentials to numerically describe vector fields on surfaces, at the expense of requiring higher-order derivatives of the approximated fields and limited to simply connected surfaces, or represent tangential tensor fields as tensor fields in 3D subjected to constraints, thus increasing the essential number of degrees of freedom. In contrast, the LMP method uses an optimal number of degrees of freedom to represent a tensor, is general with regards to the topology of the surface, and does not increase the order of the PDEs governing the tensor fields. The main idea is to construct maps between the element parametrizations and a local Monge parametrization around each node. We test the LMP method by approximating in a least-squares sense different vector and tensor fields on simply connected and genus-1 surfaces. Furthermore, we apply the LMP method to two physical models on surfaces, involving a tension-driven flow (vector-valued PDE) and nematic ordering (tensor-valued PDE), on different topologies. The LMP method thus solves the long-standing problem of the interpolation of tensors on general surfaces with an optimal number of degrees of freedom.
Abstract
We introduce a new method, the Local Monge Parametrizations (LMP) method, to approximate tensor fields on general surfaces given by a collection of local parametrizations, [...]
- 3
- read
Combined molecular/continuum modeling reveals the role of friction during fast unfolding of coiled-coil proteins
A. Torres-Sánchez, J. Vanegas, P. Purohit, M. Arroyo

Soft Matter (2019). Vol. 15, pp. 4961-4975 (Preprint)

Abstract
Coiled-coils are filamentous proteins that form the basic building block of important force-bearing cellular elements, such as intermediate filaments and myosin motors. In addition to their biological importance, coiled-coil proteins are increasingly used in new biomaterials including fibers, nanotubes, or hydrogels. Coiled-coils undergo a structural transition from an a-helical coil to an unfolded state upon extension, which allows them to sustain large strains and is critical for their biological function. By performing equilibrium and out-of-equilibrium all-atom molecular dynamics (MD) simulations of coiledcoils in explicit solvent, we show that two-state models based on Kramers’ or Bell’s theories fail to predict the rate of unfolding at high pulling rates. We further show that an atomistically informed continuum rod model accounting for phase transformations and for the hydrodynamic interactions with the solvent can reconcile two-state models with our MD results. Our results show that frictional forces, usually neglected in theories of fibrous protein unfolding, reduce the thermodynamic force acting on the interface, and thus control the dynamics of unfolding at different pulling rates. Our results may help interpret MD simulations at high pulling rates, and could be pertinent to cytoskeletal networks or protein-based artificial materials subjected to shocks or blasts.
Abstract
Coiled-coils are filamentous proteins that form the basic building block of important force-bearing cellular elements, such as intermediate filaments and myosin motors. In [...]
- 3
- read
Valoración de los ángulos del cuello del aneurisma de aorta abdominal. Estudio en 507 pacientes
C. Vaquero, L. Río, E. Norberto, N. Cenizo, J. Brizuela, M. Martín, G. Vilalta, J. Vilalta, F. Nieto, M. Pérez, E. Soudah, L. Lipsa, J. Montes

Revista Española de Investigaciones quirúrgicas (2016). Vol. 19 (4), pp. 153-156 (Preprint)

Abstract
Angulation in different planes of the neck of abdominal aortic aneurysms may be considered a limiting factor in the implantation of different prostheses in the treatment of this pathology. It is necessary to make an assessment of the angles in different planes in routine studies prior to the planning of the procedures and especially by AngioTAC. The study evaluated the measurement of 507 patients with abdominal aortic aneurysms and treated endovascular procedures and of whom the complete information was available at the level of neck angulations. In a prospective and descriptive study the situation of this aortic sector was evaluated, contributing information about the tendency in the morphological presentation of the aorta in patients with this aetiology
Abstract
Angulation in different planes of the neck of abdominal aortic aneurysms may be considered a limiting factor in the implantation of different prostheses in the treatment of [...]
- 3
- read
Robust mechanisms of ventral furrow invagination require the combination of cellular shape changes
V. Conte, J. Muñoz, B. Baum, M. Miodownik

Physical Biology (2009). Vol. 6 (1), pp. 16010-16021

Abstract
Ventral furrow formation in Drosophila is the first large-scale morphogenetic movement during the life of the embryo, and is driven by co-ordinated changes in the shape of individual epithelial cells within the cellular blastoderm. Although many of the genes involved have been identified, the details of the mechanical processes that convert local changes in gene expression into whole-scale changes in embryonic form remain to be fully understood. Biologists have identified two main cell deformation modes responsible for ventral furrow invagination: constriction of the apical ends of the cells (apical wedging) and deformation along their apical–basal axes (radial lengthening/shortening). In this work, we used a computer 2D finite element model of ventral furrow formation to investigate the ability of different combinations of three plausible elementary active cell shape changes to bring about epithelial invagination: ectodermal apical–basal shortening, mesodermal apical–basal lengthening/shortening and mesodermal apical constriction. We undertook a systems analysis of the biomechanical system, which revealed many different combinations of active forces (invagination mechanisms) were able to generate a ventral furrow. Two important general features were revealed. First that combinations of shape changes are the most robust to environmental and mutational perturbation, in particular those combining ectodermal pushing and mesodermal wedging. Second, that ectodermal pushing plays a big part in all of the robust mechanisms (mesodermal forces alone do not close the furrow), and this provides evidence that it may be an important element in the mechanics of invagination in Drosophila.
Abstract
Ventral furrow formation in Drosophila is the first large-scale morphogenetic movement during the life of the embryo, and is driven by co-ordinated changes in the [...]
- 3
- read
Cell-centred model for the simulation of curved cellular monolayers
P. Mosaffa, N. Asadipour, D. Millán, A. Rodríguez-Ferran, J. Muñoz

Computational Particle Mechanics (2015). Vol. 2 (4), pp. 359-370 (Preprint)

Abstract
This paper presents a cell-centred model for the simulation of planar and curved multicellular soft tissues. We propose a computational model that includes stress relaxation due to cell reorganisation (intercellular connectivity changes) and cytoskeleton remodelling (intracellular changes). Cells are represented by their cell centres, and their mechanical interaction is modelled through active non-linear elastic laws with a dynamically changing resting length. Special attention is paid to the handling of connectivity changes between cells, and the relaxation that the tissues exhibit under these topological changes. Cell–cell connectivity is computed by resorting to a Delaunay triangulation, which is combined with a mapping technique in order to obtain triangulations on curved manifolds. Our numerical results show that even a linear elastic cell–cell interaction model may induce a global non-linear response due to the reorganisation of the cell connectivity. This plastic-like behaviour is combined with a non-linear rheological law where the resting length depends on the elastic strain, mimicking the global visco-elastic response of tissues. The model is applied to simulate the elongation of planar and curved monolayers.
Abstract
This paper presents a cell-centred model for the simulation of planar and curved multicellular soft tissues. We propose a computational model that includes stress relaxation [...]
- 3
- read
Stress relaxation in epithelial monolayers is controlled by the actomyosin cortex
N. Khalilgharibi, J. Fouchard, N. Asadipour, R. Barrientos, M. Duda, A. Bonfanti, A. Yonis, A. Harris, P. Mosaffa, Y. Fujita, A. Kabla, Y. Mao, B. Baum, J. Muñoz, M. Miodownik, G. Charras

Nature Physics (2019). Vol. 15, pp. 839-847 (Preprint)

Abstract
Epithelial monolayers are one-cell-thick tissue sheets that line most of the body surfaces, separating internal and external environments. As part of their function, they must withstand extrinsic mechanical stresses applied at high strain rates. However, little is known about how monolayers respond to mechanical deformations. Here, by subjecting suspended epithelial monolayers to stretch, we find that they dissipate stresses on a minute timescale and that relaxation can be described by a power law with an exponential cut-off at timescales larger than about 10 s. This process involves an increase in monolayer length, pointing to active remodelling of cellular biopolymers at the molecular scale during relaxation. Strikingly, monolayers consisting of tens of thousands of cells relax stress with similar dynamics to single rounded cells, and both respond similarly to perturbations of the actomyosin cytoskeleton. By contrast, cell–cell junctional complexes and intermediate filaments do not relax tissue stress, but form stable connections between cells, allowing monolayers to behave rheologically as single cells. Taken together, our data show that actomyosin dynamics governs the rheological properties of epithelial monolayers, dissipating applied stresses and enabling changes in monolayer length.
Abstract
Epithelial monolayers are one-cell-thick tissue sheets that line most of the body surfaces, separating internal and external environments. As part of their function, they [...]
- 3
- read
Forces driving epithelial wound healing
A. Brugués, E. Anon, V. Conte, J. Veldhuis, M. Gupta, J. Colombelli, J. Muñoz, G. Brodland, B. Ladoux, X. Trepat

Natura Physics (2014). Vol. 10 (9), pp. 683-690 (Preprint)

Abstract
A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and ‘purse-string’ contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate.
Abstract
A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular [...]
- 3
- read
Simulation of intracranial aneurysm stenting: Techniques and challenges
S. Appanaboyina, F. Mut, R. Lohner, C. Putman, J. Cebral

Comput. Methods Appl. Mech. Engrg., (2009). Vol. 198 (45-46), pp. 3567-3582

Abstract
Recently, there has been considerable interest in the use of stents as endovascular flow diverters for the treatment of intracranial aneurysms. Simulating this novel method of treatment is essential for understanding the intra-aneurysmal hemodynamics in order to design better stents and to personalize and optimize the endovascular stenting procedures. This paper describes a methodology based on unstructured embedded grids for patient-specific modeling of stented cerebral aneurysms, demonstrates how the methodology can be used to address specific clinical questions, and discusses remaining technical issues. In particular, simulations are presented on a number of patient-specific models constructed from medical images and using different stent designs and treatment alternatives. Preliminary sensitivity analyses with respect to stent positioning and truncation of the stent model are presented. The results show that these simulations provide useful and valuable information that can be used during the planning phase of endovascular stenting interventions for the treatment of intracranial aneurysms.
Abstract
Recently, there has been considerable interest in the use of stents as endovascular flow diverters for the treatment of intracranial aneurysms. Simulating this novel method [...]
- 3
- read
Computational fluid dynamics of stented intracranial aneurysms using adaptive embedded unstructured grids
S. Appanaboyina, F. Mut, R. Lohner, C. Putman, J. Cebral

Int. J. Numer. Meth. Fluids (2008). Vol. 57 (5), pp. 475-493

Abstract
Recently, there has been increased interest in the use of stents as flow diverters in the endovascular treatment of cerebral aneurysms as an alternative to surgical clipping or endovascular embolization with coils. The aim of aneurysm stenting is to block the flow into the aneurysm in order to clot the blood inside the aneurysm and effectively isolate it from the circulation and prevent bleeding from the aneurysm. A hybrid meshing approach that combines body‐fitted grids for the vessels and adaptive embedded grids for the stents is proposed and analyzed. This strategy simplifies considerably the geometry modeling problem and allows accurate patient‐specific hemodynamic simulations with endovascular devices. This approach is compared with the traditional body‐fitted approach in the case of the flow around a circular cylinder at representative Reynolds number and an idealized aneurysm model with a stent. A novel technique to map different stent designs to a given patient‐specific anatomical model is presented. The methodology is demonstrated on a patient‐specific hemodynamic model of an aneurysm of the internal carotid artery constructed from a 3D rotational angiogram and stented with two different stent designs. The results show that the methodology can be successfully used to model patient‐specific anatomies with different stents thereby making it possible to explore different stent designs
Abstract
Recently, there has been increased interest in the use of stents as flow diverters in the endovascular treatment of cerebral aneurysms as an alternative to surgical clipping [...]
- 3
- read
Analytical and numerical analysis of human dental occlusal contact
F. Bastos, E. Casas, S. Oller

Computer Methods in Biomechanics and Biomedical Engineering (2013). Vol. 16 (5), pp. 495-503

Abstract
The knowledge of contact forces in teeth surfaces during mastication or para-functional movements can help to understand processes related to friction and wear of human dental enamel. The development of a numerical model for analysis of the occlusal contact between two antagonistic teeth is proposed, which includes three basic steps: the characterisation of the surface roughness, its homogenisation using an assumed distribution function and the numerical determination of the resulting forces. Finite element strain results for the main different asperities are statistically combined, deriving the predicted macroscopic behaviour of the interface. Axisymmetric and 3D numerical models with an elasto-plastic constitutive law are used to simulate micro-indentations and micro-contacts, respectively. The contact is allowed to occur locally in planes not necessarily parallel to the surface's mean plane, a problem for which there is no analytical solution. The three identified parameters, homogenised surface hardness (3.68 GPa), surface yield stress (3.08 GPa) and static friction coefficient (0.23), agree with the experimental values reported in the literature.
Abstract
The knowledge of contact forces in teeth surfaces during mastication or para-functional movements can help to understand processes related to friction and wear of human dental [...]
- 2
- read
A homeostatic-driven turnover remodelling constitutive model for healing in soft tissues
E. Comellas, T. Gasser, F. Bellomo, S. Oller

Journal of the Royal Society Interface (2016). (preprint) Vol. 13 (116), pp. 1-14

Abstract
All rights reserved. Remodelling of soft biological tissue is characterized by interacting biochemical and biomechanical events, which change the tissue's microstructure, and, consequently, its macroscopic mechanical properties. Remodelling is a well-defined stage of the healing process, and aims at recovering or repairing the injured extracellular matrix. Like other physiological processes, remodelling is thought to be driven by homeostasis, i.e. it tends to re-establish the properties of the uninjured tissue. However, homeostasis may never be reached, such that remodelling may also appear as a continuous pathological transformation of diseased tissues during aneurysm expansion, for example. A simple constitutive model for soft biological tissues that regards remodelling as homeostatic-driven turnover is developed. Specifically, the recoverable effective tissue damage, whose rate is the sum of a mechanical damage rate and a healing rate, serves as a scalar internal thermodynamic variable. In order to integrate the biochemical and biomechanical aspects of remodelling, the healing rate is, on the one hand, driven by mechanical stimuli, but, on the other hand, subjected to simple metabolic constraints. The proposed model is formulated in accordance with continuum damage mechanics within an open-system thermodynamics framework. The numerical implementation in an in-house finite-element code is described, particularized for Ogden hyperelasticity. Numerical examples illustrate the basic constitutive characteristics of the model and demonstrate its potential in representing aspects of remodelling of soft tissues. Simulation results are verified for their plausibility, but also validated against reported experimental data. Remodelling of soft biological tissue is characterized by interacting biochemical and biomechanical events, which change the tissue's microstructure, and, consequently, its macroscopic mechanical properties. Remodelling is a well-defined stage of the healing process, and aims at recovering or repairing the injured extracellular matrix. Like other physiological processes, remodelling is thought to be driven by homeostasis, i.e. it tends to re-establish the properties of the uninjured tissue. However, homeostasis may never be reached, such that remodelling may also appear as a continuous pathological transformation of diseased tissues during aneurysm expansion, for example. A simple constitutive model for soft biological tissues that regards remodelling as homeostatic-driven turnover is developed. Specifically, the recoverable effective tissue damage, whose rate is the sum of a mechanical damage rate and a healing rate, serves as a scalar internal thermodynamic variable. In order to integrate the biochemical and biomechanical aspects of remodelling, the healing rate is, on the one hand, driven by mechanical stimuli, but, on the other hand, subjected to simple metabolic constraints. The proposed model is formulated in accordance with continuum damage mechanics within an open-system thermodynamics framework. The numerical implementation in an in-house finite-element code is described, particularized for Ogden hyperelasticity. Numerical examples illustrate the basic constitutive characteristics of the model and demonstrate its potential in representing aspects of remodelling of soft tissues. Simulation results are verified for their plausibility, but also validated against reported experimental data.
Abstract
All rights reserved. Remodelling of soft biological tissue is characterized by interacting biochemical and biomechanical events, which change the tissue's microstructure, [...]
- 2
- read
A constitutive model for tissue adaptation: Necrosis and stress driven growth
F. Bellomo, F. Armero, L. Nallim, S. Oller

Mechanics Research Communications (2012). Vol. 42 (SI), pp. 51-59

Abstract
This paper presents a general constitutive model for tissue stress driven growth and necrotic remodeling. The general theoretical framework is given by a kinematics formulation in large strain. The model allows the analysis of tissue behaviour considering the coupling of biological and mechanical fields, through the implementation of an internal variable that represents the bioavailability, together with the growth induced by mechanical stimuli. To take into account the tissue necrosis phenomenon a reinterpretation of the classical theory of mixtures is proposed. The proposed formulation is based on the consideration of two components, normal tissue and necrotic tissue, each one with its own volumetric participation, which is treated in an evolutive way, allowing simulating the phenomena of ischemia. This article also presents a brief description of the numerical implementation of the model as well as the obtained results, which shows the process of necrosis of part of the tissue, its influence on the surrounding healthy tissue, and the interaction between the nutrients availability and the stress driven growth and necrotic remodeling process.
Abstract
This paper presents a general constitutive model for tissue stress driven growth and necrotic remodeling. The general theoretical framework is given by a kinematics formulation [...]
- 2
- read
Computational evaluation of cochlear implant surgery outcomes accounting for uncertainty and parameter variability
N. Mangado, J. Pons Prats, M. Coma, P. Mistrik, G. Piella, M. Ceresa, M. Ballester

Frontiers in Physiology (2018). Vol. 9, pp. 1-14

Abstract
Cochlear implantation (CI) is a complex surgical procedure that restores hearing in patients with severe deafness. The successful outcome of the implanted device relies on a group of factors, some of them unpredictable or difficult to control. Uncertainties on the electrode array position and the electrical properties of the bone make it difficult to accurately compute the current propagation delivered by the implant and the resulting neural activation. In this context, we use uncertainty quantification methods to explore how these uncertainties propagate through all the stages of CI computational simulations. To this end, we employ an automatic framework, encompassing from the finite element generation of CI models to the assessment of the neural response induced by the implant stimulation. To estimate the confidence intervals of the simulated neural response, we propose two approaches. First, we encode the variability of the cochlear morphology among the population through a statistical shape model. This allows us to generate a population of virtual patients using Monte Carlo sampling and to assign to each of them a set of parameter values according to a statistical distribution. The framework is implemented and parallelized in a High Throughput Computing environment that enables to maximize the available computing resources. Secondly, we perform a patient-specific study to evaluate the computed neural response to seek the optimal post-implantation stimulus levels. Considering a single cochlear morphology, the uncertainty in tissue electrical resistivity and surgical insertion parameters is propagated using the Probabilistic Collocation method, which reduces the number of samples to evaluate. Results show that bone resistivity has the highest influence on CI outcomes. In conjunction with the variability of the cochlear length, worst outcomes are obtained for small cochleae with high resistivity values. However, the effect of the surgical insertion length on the CI outcomes could not be clearly observed, since its impact may be concealed by the other considered parameters. Whereas the Monte Carlo approach implies a high computational cost, Probabilistic Collocation presents a suitable trade-off between precision and computational time. Results suggest that the proposed framework has a great potential to help in both surgical planning decisions and in the audiological setting process.
Abstract
Cochlear implantation (CI) is a complex surgical procedure that restores hearing in patients with severe deafness. The successful outcome of the implanted device relies on [...]
- 2
- read
Hydraulic fracture during epithelial stretching
L. Casares, R. Vincent, D. Zalvidea, N. Campillo, D. Navajas, M. Arroyo, X. Trepat

Nature materials (2015). Vol. 14 (3), pp. 343-351

Abstract
The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells' cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres. After pressure equilibration, cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics.
Abstract
The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells' cytoskeleton, in the plasma membrane, or in [...]
- 2
- read
Reverse engineering the euglenoid movement
M. Arroyo, L. Heltai, D. Millán, A. DeSimone

Proceedings of the National Academy of Sciences of the United States of America (2012). Vol. 109 (44), pp. 17874-17879

Abstract
Euglenids exhibit an unconventional motility strategy amongst unicellular eukaryotes, consisting of large-amplitude highly concerted deformations of the entire body (euglenoid movement or metaboly). A plastic cell envelope called pellicle mediates these deformations. Unlike ciliary or flagellar motility, the biophysics of this mode is not well understood, including its efficiency and molecular machinery. We quantitatively examine video recordings of four euglenids executing such motions with statistical learning methods. This analysis reveals strokes of high uniformity in shape and pace. We then interpret the observations in the light of a theory for the pellicle kinematics, providing a precise understanding of the link between local actuation by pellicle shear and shape control. We systematically understand common observations, such as the helical conformations of the pellicle, and identify previously unnoticed features of metaboly. While two of our euglenids execute their stroke at constant body volume, the other two exhibit deviations of about 20% from their average volume, challenging current models of low Reynolds number locomotion. We find that the active pellicle shear deformations causing shape changes can reach 340%, and estimate the velocity of the molecular motors. Moreover, we find that metaboly accomplishes locomotion at hydrodynamic efficiencies comparable to those of ciliates and flagellates. Our results suggest new quantitative experiments, provide insight into the evolutionary history of euglenids, and suggest that the pellicle may serve as a model for engineered active surfaces with applications in microfluidics.
Abstract
Euglenids exhibit an unconventional motility strategy amongst unicellular eukaryotes, consisting of large-amplitude highly concerted deformations of the entire body (euglenoid [...]
- 2
- read
Shape dynamics, lipid hydrodynamics, and the complex viscoelasticity of bilayer membranes
M. Rahimi, M. Arroyo

Physical review E: statistical, nonlinear and soft matter physics (2012). Vol. 86 (1), pp. 1-15

Abstract
Biological membranes are continuously brought out of equilibrium, as they shape organelles, package and transport cargo, or respond to external actions. Even the dynamics of plain lipid membranes in experimental model systems are very complex due to the tight interplay between the bilayer architecture, the shape dynamics, and the rearrangement of the lipid molecules. We formulate and numerically implement a continuum model of the shape dynamics and lipid hydrodynamics, which describes the bilayer by its midsurface and by a lipid density field for each monolayer. The viscoelastic response of bilayers is determined by the stretching and curvature elasticity, and by the inter-monolayer friction and the membrane interfacial shear viscosity. While the bilayer equilibria are well understood theoretically, dynamical calculations have relied on simplified continuum approaches of uncertain transferability, or on molecular simulations reaching very limited length and time scales. Our approach incorporates the main physics, is fully nonlinear, does not assume predefined shapes, and can access a wide range of time and length scales. We validate it with the well understood tether extension. We investigate the tubular lipid transport between cells, the dynamics of bud absorption by a planar membrane, and the fate of a localized lipid density asymmetry in vesicles. These axisymmetric examples bear biological relevance and highlight the diversity of dynamical regimes that bilayers can experience.
Abstract
Biological membranes are continuously brought out of equilibrium, as they shape organelles, package and transport cargo, or respond to external actions. Even the dynamics [...]
- 2
- read
Importance of force decomposition for local stress calculations in biomembrane molecular simulations
J. Vanegas, A. Torres-Sánchez, M. Arroyo

Journal of chemical theory and computation (2014). Vol. 10 (2), pp. 691-702 (preprint)

Abstract
Local stress fields are routinely computed from molecular dynamics trajectories to understand the structure and mechanical properties of lipid bilayers. These calculations can be systematically understood with the Irving-Kirkwood-Noll theory. In identifying the stress tensor, a crucial step is the decomposition of the forces on the particles into pairwise contributions. However, such a decomposition is not unique in general, leading to an ambiguity in the definition of the stress tensor, particularly for multibody potentials. Furthermore, a theoretical treatment of constraints in local stress calculations has been lacking. Here, we present a new implementation of local stress calculations that systematically treats constraints and considers a privileged decomposition, the central force decomposition, that leads to a symmetric stress tensor by construction. We focus on biomembranes, although the methodology presented here is widely applicable. Our results show that some unphysical behavior obtained with previous implementations (e.g. nonconstant normal stress profiles along an isotropic bilayer in equilibrium) is a consequence of an improper treatment of constraints. Furthermore, other valid force decompositions produce significantly different stress profiles, particularly in the presence of dihedral potentials. Our methodology reveals the striking effect of unsaturations on the bilayer mechanics, missed by previous stress calculation implementations.
Abstract
Local stress fields are routinely computed from molecular dynamics trajectories to understand the structure and mechanical properties of lipid bilayers. These calculations [...]
- 2
- read
Smart helical structures inspired by the pellicle of euglenids
G. Noselli, M. Arroyo, A. DeSimone

Journal of the Mechanics and Physics of Solids (2019). Vol. 123, pp. 234-246 (Preprint)

Abstract
This paper deals with a concept for a reconfigurable structure bio-inspired by the cell wall architecture of euglenids, a family of unicellular protists, and based on the relative sliding of adjacent strips. Uniform sliding turns a cylinder resulting from the assembly of straight and parallel strips into a cylinder of smaller height and larger radius, in which the strips are deformed into a family of parallel helices. We examine the mechanics of this cylindrical assembly, in which the interlocking strips are allowed to slide freely at their junctions, and compute the external forces (axial force and axial torque at the two ends, or pressure on the lateral surface) necessary to drive and control the shape changes of the composite structure. Despite the simplicity of the structure, we find a remarkably complex mechanical behaviour that can be tuned by the spontaneous curvature or twist of the strips.
Abstract
This paper deals with a concept for a reconfigurable structure bio-inspired by the cell wall architecture of euglenids, a family of unicellular protists, and based on the [...]
- 2
- read
Hemodynamic features associated with abdominal aortic aneurysm (AAA) geometry
G. Vilalta, E. Soudah, J. Vilalta, F. Nieto, M. Bordone, M. Pérez, C. Vaquero

Journal of Biomechanics (2012). Vol. 45 (S1), p.S37

Abstract
Recent findings have shown that maximum diameter of abdominal aortic aneurysm (AAA) and its growth rate are not entirely reliable indicators of rupture potential. The AAA geometrical shape and size may be related to the rupture risk which is a clinical manifestation of the balance between the forces generated by blood flow within the AAA and its strength. This study aims at assessing the hemodynamic features associated with the geometry of AAAs.
Abstract
Recent findings have shown that maximum diameter of abdominal aortic aneurysm (AAA) and its growth rate are not entirely reliable indicators of rupture potential. The [...]
- 2
- read
CFD modelling of abdominal aortic aneurysm on hemodynamic loads using a realistic geometry with CT
E. Soudah, E. Kwee, T. Loong, M. Bordone, U. Pua, S. Narayanan

Computational and Mathematical Methods in Medicine (2013). Vol. 2013 (472564), pp. 1-9

Abstract
The objective of this study is to find a correlation between the abdominal aortic aneurysm (AAA) geometric parameters, wall stress shear (WSS), abdominal flow patterns, intraluminal thrombus (ILT), and AAA arterial wall rupture using computational fluid dynamics (CFD). Real AAA 3D models were created by three-dimensional (3D) reconstruction of in vivo acquired computed tomography (CT) images from 5 patients. Based on 3D AAA models, high quality volume meshes were created using an optimal tetrahedral aspect ratio for the whole domain. In order to quantify the WSS and the recirculation inside the AAA, a 3D CFD using finite elements analysis was used. The CFD computation was performed assuming that the arterial wall is rigid and the blood is considered a homogeneous Newtonian fluid with a density of 1050¿kg/m3 and a kinematic viscosity of Pa·s. Parallelization procedures were used in order to increase the performance of the CFD calculations. A relation between AAA geometric parameters (asymmetry index (ß), saccular index (¿), deformation diameter ratio (¿), and tortuosity index (e)) and hemodynamic loads was observed, and it could be used as a potential predictor of AAA arterial wall rupture and potential ILT formation.
Abstract
The objective of this study is to find a correlation between the abdominal aortic aneurysm (AAA) geometric parameters, wall stress shear (WSS), abdominal flow patterns, [...]
- 2
- read
Study of angulations of visceral abdominals arteries in their abdominal aorta emergency
C. Vaquero, G. Vilalta, J. Vilalta, F. Nieto, M. Pérez, E. , E. Soudah, L. Lipsa, L. Río, E. Norberto, N. Cenizo, J. Brizuela, M. Martín, J. Montes

Revista Iberoaméricana de Cirugía Vascular (2016). Vol. 4 (4), pp. 184-189 (Preprint)

Abstract
Recently, fenestrated, branched and stent grafts have been developed in order to treat endovascular aneurysmal pathology at the level of the aorta in the emergence of the visceral arteries. For the implantation of stents, it is necessary to have a precise planimetry of the origin and orientation of the visceral branches in order firstly to perform the correct manufacture of the endoprosthesis and secondly the placement with precision of the same. The knowledge of the emergency of the vessels of the aortic wall and its orientation knowing the angle of emergency. The data obtained for the planning of the endovascular treatment of 37 patients in order to obtain data from the descriptive point of view of this sector.
Abstract
Recently, fenestrated, branched and stent grafts have been developed in order to treat endovascular aneurysmal pathology at the level of the aorta in the emergence of the [...]
- 2
- read
Development of a predictive model of radiological damage in patients with rheumatoid arthritis based on artificial intelligence
J. Lezcano, J. Ivorra-Cortes, R. López, J. Martín, B. Fernando-Gutiérrez, M. González-Gay, A. Balsa, I. González-Álvaro, F. Salazar, L. Abásolo, L. Rodríguez-Rodríguez

Annals of the Rheumatic Diseases (2018). Vol. 77 (S2), pp. 215

Abstract
Background Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased mortality and disability. Although different factors associated with prognosis have been identified, it is still difficult to predict the evolution of a specific patient. Objectives Our objective is to train and validate a predictive model of disease severity using radiological damage as a surrogate marker, based on Artificial Intelligence techniques, and using clinical and genetic data. Methods Four independent cohorts were included (892 patients with 1667 hand X-rays). Radiological damage was measured with the Sharp/van-der-Heijde score (SvdH). The variables to be predicted [total value of SvdH, erosion component (ES) and joint narrowing (NS)] were logarithmically transformed. As clinical predictors, age at onset of symptoms, sex, duration of the disease at the time of each radiograph, year of onset of symptoms and presence of rheumatoid factor were used. As genetic variables, the single nucleotide polymorphism data obtained from the Immunochip genotyping platform (Illumina) were used. In addition, an interaction between each polymorphism and the duration of the disease was introduced. Three cohorts were used for the selection of variables, generation of predictive models and internal validation. The fourth cohort was used to perform the external validation of the models. Regression trees with random effects were generated using the R package ‘REEMtree’. The goodness of fit of the models was measured using the root mean squared error (RMSE) and the intraclass correlation coefficient (ICC). Results In the cohorts where the predictive models were developed, the RMSEs for total SvdH, ES and NS were 3.16, 1.02 and 2.29 units of the Sharp/van-der-Heijde score, respectively. The ICCs were 0.96, 0.87 and 0.95, respectively. In the external validation cohort, the RMSEs were 7.13, 3.53 and 4.81 units of the Sharp/van-der-Heijde score, respectively. The ICCs were 0.90, 0.78 and 0.88. For the total SvdH, the best fit model contained the variables ‘age of onset of the symptoms of RA’ and the interaction between duration of the disease and 3 polymorphisms: rs10752907, rs4405161 and rs2501617. For the ES, it contained the variables ‘age of onset of AR symptoms’, the polymorphism rs7769752 and the interaction between disease duration and 6 polymorphisms: rs12410412, rs117029499, rs72925969, rs869186, rs11258464, rs4781952. For the NS, it contained the variables ‘age of onset of AR symptoms’, ‘gender’, and the interaction between disease duration and 9 polymorphisms: rs3814055, rs1020822, rs13157991, rs152294, rs2914190, rs10824537, rs2637229, rs114136906 and rs4958241. Conclusions It is possible to generate predictive models of radiological damage of great precision using Artificial Intelligence techniques. This could allow early stratification of patients according to prognosis. It is necessary to validate these models in other populations
Abstract
Background Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased mortality and disability. Although different factors associated with prognosis [...]
- 2
- read
A biomechanical analysis of ventral furrow formation in the Drosophila melanogaster embryo
V. Conte, F. Ulrich, B. Baum, J. Muñoz, J. Veldhuis, W. Brodland, M. Miodownik

PloS One (2012). Vol. 7 (4), pp. 1-17

Abstract
The article provides a biomechanical analysis of ventral furrow formation in the Drosophila melanogaster embryo. Ventral furrow formation is the first large-scale morphogenetic movement in the fly embryo. It involves deformation of a uniform cellular monolayer formed following cellularisation, and has therefore long been used as a simple system in which to explore the role of mechanics in force generation. Here we use a quantitative framework to carry out a systematic perturbation analysis to determine the role of each of the active forces observed. The analysis confirms that ventral furrow invagination arises from a combination of apical constriction and apical–basal shortening forces in the mesoderm, together with a combination of ectodermal forces. We show that the mesodermal forces are crucial for invagination: the loss of apical constriction leads to a loss of the furrow, while the mesodermal radial shortening forces are the primary cause of the internalisation of the future mesoderm as the furrow rises. Ectodermal forces play a minor but significant role in furrow formation: without ectodermal forces the furrow is slower to form, does not close properly and has an aberrant morphology. Nevertheless, despite changes in the active mesodermal and ectodermal forces lead to changes in the timing and extent of furrow, invagination is eventually achieved in most cases, implying that the system is robust to perturbation and therefore over-determined.
Abstract
The article provides a biomechanical analysis of ventral furrow formation in the Drosophila melanogaster embryo. Ventral furrow formation is the first large-scale [...]
- 2
- read
A 3D finite element model of ventral furrow invagination in the Drosophila melanogaster embryo
V. Conte, J. Muñoz, M. Miodownik

Journal of the Mechanical Behavior of Biomedical Materials (2008). Vol. 1 (2), pp. 188-198

Abstract
The paper describes a mechanical model of epithelial tissue development in Drosophila embryos to investigate a buckling phenomenon called invagination. The finite element method is used to model this ventral furrow formation in 3D by decomposing the total deformation into two parts: an imposed active deformation, and an elastic passive deformation superimposed onto the latter. The model imposes as boundary conditions (i) a constant yolk volume and (ii) a sliding contact condition of the cells against the vitelline membrane, which is interpolated as a B-Spline surface. The active deformation simulates the effects of apical constriction and apico-basal elongation of cells. This set of local cellular mechanisms leads to global shape changes of the embryo which are associated with known gene expressions. Using the model we have tested different plausible hypotheses postulated to account for the mechanical behaviour of epithelial tissues. In particular, we conclude that only certain combinations of local cell shape change can successfully reproduce the invagination process. We have quantitatively compared the model with a 2D model and shown that it exhibits a more robust invagination phenomenon. The 3D model has also revealed that invagination causes a yolk flow from the central region to the anterior and posterior ends of the embryo, causing an accordion-like global compression and expansion wave to move through the embryo. Such a phenomenon cannot be described by 2D models.
Abstract
The paper describes a mechanical model of epithelial tissue development in Drosophila embryos to investigate a buckling phenomenon called invagination. The finite [...]
- 2
- read
Porous-based rheological model for tissue fluidisation
N. Asadipour, X. Trepat, J. Muñoz

Journal of the Mechanics and Physics of Solids (2016). Vol. 96, pp. 535-549 (Preprint)

Abstract
It has been experimentally observed that cells exhibit a fluidisation process when subjected to a transient stretch, with an eventual recovery of the mechanical properties upon removal of the applied deformation. This fluidisation process is characterised by a decrease of the storage modulus and an increase of the phase angle. We propose a rheological model which is able to reproduce this combined mechanical response. The model is described in the context of continua and adapted to a cell-centred particle system that simulates cell–cell interactions. Mechanical equilibrium is coupled with two evolution laws: (i) one for the reference configuration, and (ii) another for the porosity or polymer density. The first law depends on the actual strain of the tissue, while the second assumes different remodelling rates during porosity increase and decrease. The theory is implemented on a particle based model and tested on a stretching experiment. The numerical results agree with the experimental measurements for different stretching magnitudes
Abstract
It has been experimentally observed that cells exhibit a fluidisation process when subjected to a transient stretch, with an eventual recovery of the mechanical [...]
- 2
- read
Non-regularised inverse finite element analysis for 3D traction force microscopy
J. Muñoz

Int. J. Numer. Anal. Model. (2016). Vol. 13 (5), pp. 763-781 (Preprint)

Abstract
The tractions that cells exert on a gel substrate from the observed displacements is an increasingly attractive and valuable information in biomedical experiments. The computation of these tractions requires in general the solution of an inverse problem. Here, we resort to the discretisation with finite elements of the associated direct variational formulation, and solve the inverse analysis using a least square approach. This strategy requires the minimisation of an error functional, which is usually regularised in order to obtain a stable system of equations with a unique solution. In this paper we show that for many common three-dimensional geometries, meshes and loading conditions, this regularisation is unnecessary. In these cases, the computational cost of the inverse problem becomes equivalent to a direct finite element problem. For the non-regularised functional, we deduce the necessary and sufficient conditions that the dimensions of the interpolated displacement and traction fields must preserve in order to exactly satisfy or yield a unique solution of the discrete equilibrium equations. We apply the theoretical results to some illustrative examples and to real experimental data. Due to the relevance of the results for biologists and modellers, the article concludes with some practical rules that the finite element discretisation must satisfy.
Abstract
The tractions that cells exert on a gel substrate from the observed displacements is an increasingly attractive and valuable information in biomedical experiments. The computation [...]
- 2
- read
Hybrid cell-centred/vertex model for multicellular systems with equilibrium-preserving remodelling
P. Mosaffa, A. Rodríguez-Ferran, J. Muñoz

Int. J. Numer. Meth. Bio. Engng. (2018). Vol. 34 (3), pp. 1-33 (Preprint)

Abstract
We present a hybrid cell‐centred/vertex model for mechanically simulating planar cellular monolayers undergoing cell reorganisation. Cell centres are represented by a triangular nodal network, while the cell boundaries are formed by an associated vertex network. The two networks are coupled through a kinematic constraint which we allow to relax progressively. Special attention is paid to the change of cell‐cell connectivity due to cell reorganisation or remodelling events. We handle these situations by using a variable resting length and applying an Equilibrium‐Preserving Mapping on the new connectivity, which computes a new set of resting lengths that preserve nodal and vertex equilibrium. We illustrate the properties of the model by simulating monolayers subjected to imposed extension and during a wound healing process. The evolution of forces and the Equilibrium‐Preserving Mapping are analysed during the remodelling events. As a by‐product, the proposed technique enables to recover fully vertex or fully cell‐centred models in a seamless manner by modifying a numerical parameter of the model.
Abstract
We present a hybrid cell‐centred/vertex model for mechanically simulating planar cellular monolayers undergoing cell reorganisation. Cell centres are represented by a triangular [...]
- 2
- read
Computational modeling of epithelial wound healing: Short and long term chemo-mechanical mechanisms
L. Roldán, J. Muñoz, P. Sáez

Comput. Methods Appl. Mech. Engrg., (2019). Vol. 350, pp. 28-56

Abstract
During the lifetime of all living multicellular organisms, wounds in their tissues are frequently observed. The capability of closing those gaps is fundamental for a healthy development. If done deficiently, many diseases may occur from simple inflammation to tumor formation. The wound healing process in epithelial tissue occurs in three different stages. The first one is the assembly of a supra-cellular actomyosin cable and its migration towards the wound edge, triggered by biochemical processes in which calcium plays a distinctive role. How this process is orchestrated following damage remains unclear. Later, after its positioning, the cable contracts driving the tissue towards the gap and reducing the wound area. Finally, cell migration towards the interior of the wound ends up sealing the tissue. In this work, we make use of a mechanical continuum model for the first two stages in order to developed and 2D finite element simulations within a monolithically fully implicit implementation. The model for the actomyosin cable formation involves the coupling of transient calcium ions transport, with actin fibers and myosin motors recruitment and non-linear mechanical response of the tissue. The contraction stage, the active deformation of the previously formed actomyosin cable is taken into account. The relative motion of the myosin motors over the actin filaments is modeled so there exists an active tissue contraction in the direction of those fibers. Upon implementation, the model is capable of performing a wide range of biophysical situations reported experimentally, as we demonstrate in our numerical results. We have been able to rationalize through computational mechanics the firing of calcium in the wound right after damage infliction as well as the consequent formation of actin ring, reproducing nicely what has been reported in biological literature. Thereafter, the numerical model of acto-myosin contraction, fully integrated with the non-linear mechanics of the problem, correlates with the mechanics of wound closure at the actin-ring contraction stage. More importantly, the approach is the first of its kind in the modeling of epithelial and embryonic cell layers, where a wide number of complex mechanics has been integrated and solved though computational methods in engineering. We believe that the simulations will help to unravel new insights in open questions of developmental biology.
Abstract
During the lifetime of all living multicellular organisms, wounds in their tissues are frequently observed. The capability of closing those gaps is fundamental [...]
- 2
- read
Mechanistic studies on the self-assembly of PLGA patchy particles and their potential applications in biomedical imaging
C. Salvador-Morales, B. Brahmbhatt, V. Márquez-Miranda, I. Araya-Dura, J. Canan, F. González-Nilo, C. Vilos, J. Cebral, F. Mut, R. Lohner, B. Leong, G. Sundaresan, J. Zweit

Langmuir (2016). Vol. 32 (31), pp. 7929-7949

Abstract
Currently, several challenges prevent poly(lactic-co-glycolic acid) (PLGA) particles from reaching clinical settings. Among these is a lack of understanding of the molecular mechanisms involved in the formation of these particles. We have been studying in depth the formation of patchy polymeric particles. These particles are made of PLGA and lipid–polymer functional groups. They have unique patch–core–shell structural features: hollow or solid hydrophobic cores and a patchy surface. Previously, we identified the shear stress as the most important parameter in a patchy particle’s formation. Here, we investigated in detail the role of shear stress in the patchy particle’s internal and external structure using an integrative experimental and computational approach. By cross-sectioning the multipatch particles, we found lipid-based structures embedded in the entire PLGA matrix, which represents a unique finding in the PLGA field. By developing novel computational fluid dynamics and molecular dynamics simulations, we found that the shear stress determines the internal structure of the patchy particles. Equally important, we discovered that these particles emit a photoacoustic (PA) signal in the optical clinical imaging window. Our results show that particles with multiple patches emit a higher PA signal than single-patch particles. This phenomenon most likely is due to the fact that multipatchy particles absorb more heat than single-patchy particles as shown by differential scanning calorimetry analysis. Furthermore, we demonstrated the use of patchy polymeric particles as photoacoustic molecular probes both in vitro and in vivo studies. The fundamental studies described here will help us to design more effective PLGA carriers for a number of medical applications as well as to accelerate their medical translation.
Abstract
Currently, several challenges prevent poly(lactic-co-glycolic acid) (PLGA) particles from reaching clinical settings. Among these is a lack of understanding of the [...]
- 2
- read
Perspectives on Sharing Models and Related Resources in Computational Biomechanics Research
A. Erdemir, P. Hunter, G. Holzapfel, L. Loew, J. Middleton, C. Jacobs, P. Nithiarasu, R. Lohner, G. Wei, B. Winkelstein, V. Barocas, F. Guilak, J. Ku, J. Hicks, S. Delp, M. Sacks, J. Weiss, G. Ateshian, S. Mass, A. McCulloch, G. Peng

Journal of Biomechanics Engineering (2018). Vol. 140 (2), pp. 1-11

Abstract
The role of computational modeling for biomechanics will be increasingly prominent. In computational biomechanics, model sharing can facilitate assessment of reproducibility, and can provide an opportunity for repurposing and reuse, and a venue for medical training. The community's desire to investigate biological and biomechanical phenomena crossing multiple systems, scales, and physical domains, also motivates sharing of modeling resources as blending of models developed by domain experts is anticipated. The goal of this article is to understand current perspectives in the biomechanics community for the sharing of computational models and related resources. Opinions on opportunities, challenges, and pathways to model sharing, particularly as part of the scholarly publishing workflow, were sought. A synthesis of these opinion pieces indicates that the community recognizes the necessity and usefulness of model sharing. There is a strong will to facilitate model sharing and there are corresponding initiatives by the scientific journals. Outside the publishing enterprise, infrastructure to facilitate model sharing in biomechanics exists and simulation software developers are interested in accommodating the community's needs for sharing of modeling resources. Encouragement for the use of standardized markups, concerns related to quality assurance, acknowledgement of increased burden, and importance of stewardship of resources are noted. In the short-term, it is advisable that the community builds upon recent strategies and experiments with new pathways for continued demonstration of model sharing, its promotion, and its utility. Nonetheless, the need for a long term strategy to unify approaches in sharing computational models and related resources is acknowledged.
Abstract
The role of computational modeling for biomechanics will be increasingly prominent. In computational biomechanics, model sharing can facilitate assessment of reproducibility, [...]
- 2
- read
Efficient simulation of blood flow past complex endovascular devices using an adaptive embedding technique
J. Cebral, R. Lohner

IEEE Transactions on Intelligent Transportation Systems (2005). Vol. 24 (4), pp. 468-476

Abstract
The simulation of blood flow past endovascular devices such as coils and stents is a challenging problem due to the complex geometry of the devices. Traditional unstructured grid computational fluid dynamics relies on the generation of finite element grids that conform to the boundary of the computational domain. However, the generation of such grids for patient-specific modeling of cerebral aneurysm treatment with coils or stents is extremely difficult and time consuming. This paper describes the application of an adaptive grid embedding technique previously developed for complex fluid structure interaction problems to the simulation of endovascular devices. A hybrid approach is used: the vessel walls are treated with body conforming grids and the endovascular devices with an adaptive mesh embedding technique. This methodology fits naturally in the framework of image-based computational fluid dynamics and opens the door for exploration of different therapeutic options and personalization of endovascular procedures.
Abstract
The simulation of blood flow past endovascular devices such as coils and stents is a challenging problem due to the complex geometry of the devices. Traditional unstructured [...]
- 2
- read
Applications of patient-specific CFD in medicine and life science
R. Lohner, J. Cebral, O. Soto, P. Yim, J. Burgess

Int. J. Numer. Meth. Fluids (2003). Vol. 43 (6-7), pp. 637-650

Abstract
Recent advances in medical image segmentation, grid generation, flow solvers, realistic boundary conditions, fluid–structure interaction, data reduction and visualization arc reviewed with special emphasis on patient‐specific flow prediction. At the same time, present shortcomings in each one of these areas are identified. Several examples are given that show that this methodology is maturing rapidly, and may soon find widespread use in medicine.
Abstract
Recent advances in medical image segmentation, grid generation, flow solvers, realistic boundary conditions, fluid–structure interaction, data reduction and visualization [...]
- 2
- read
Blood Flow Modeling in Carotid Arteries with Computational Fluid Dynamics and MR Imaging
J. Cebral, P. Yim, R. Lohner, O. Soto, P. Choyke

Academic Radiology (2002). Vol. 9 (11), pp. 1286-1299

Abstract
The authors' goal was to develop a noninvasive method for detailed assessment of blood flow patterns from direct in vivo measurements of vessel anatomy and flow rates. The authors developed a method to construct realistic patient-specific finite element models of blood flow in carotid arteries. Anatomic models are reconstructed from contrast material-enhanced magnetic resonance (MR) angiographic images with a tubular deformable model along each arterial branch. A surface-merging algorithm is used to create a watertight model of the carotid bifurcation for subsequent finite element grid generation, and a fully implicit scheme is used to solve the incompressible Navier-Stokes equations on unstructured grids. Physiologic boundary conditions are derived from cine phase-contrast MR flow velocity measurements at two locations below and above the bifurcation. Vessel wall compliance is incorporated by means of fluid-solid interaction algorithms. The method was tested on imaging data from a healthy subject and a patient with mild stenosis. Finite element grids were successfully generated, and pulsatile blood flow calculations were performed. Computed and measured velocity profiles show good agreement. Flow patterns and wall shear stress distributions were visualized. Patient-specific computational fluid dynamics modeling based on MR images can be performed robustly and efficiently. Preliminary validation studies in a physical flow-through model suggest that the model is accurate. This method can be used to characterize blood flow patterns in healthy and diseased arteries and may eventually help physicians to supplement imaging-based diagnosis and predict and evaluate the outcome of interventional procedures.
Abstract
The authors' goal was to develop a noninvasive method for detailed assessment of blood flow patterns from direct in vivo measurements of vessel anatomy and flow rates. [...]
- 2
- read
An inverse approach for the mechanical characterisation of vascular tissues via a generalised rule of mixtures
F. Bellomo, S. Oller, L. Nallim

Computer Methods in Biomechanics and Biomedical Engineering (2012). Vol. 15 (12), pp. 1257-1262

Abstract
Mechanical factors such as stresses and strains play a major role in the growth and remodelling of soft biological tissues. The main constituents of tissue undergo different processes reacting to mechanical stimulus. Thereby, the characterisation of growth and remodelling requires an accurate estimation of the stresses and strains of their main components. Many soft tissues can be considered as composite materials and can be analysed using an appropriate rule of mixtures. Particularly, arterial tissue can be modelled as an isotropic soft matrix reinforced with preferentially oriented collagen fibres. An inverse approach to obtain the mechanical characterisation of each main component is proposed in this work. The procedure is based on a rule of mixtures raised in a finite deformation framework and generalised to include kinematics and compatibility equations for serial–parallel behaviour. This methodology allows obtaining the stress–strain relationship of the components fitting experimental data.
Abstract
Mechanical factors such as stresses and strains play a major role in the growth and remodelling of soft biological tissues. The main constituents of tissue undergo different [...]
- 1
- read
On the feasibility of the computational modelling of the endoluminal vacuum-assisted closure of an oesophageal anastomotic leakage
E. Comellas, F. Bellomo, I. Rosales, L. Castilo, R. Sánchez, P. Turon, S. Oller

Royal Society Open Science (2018). Vol. 5 (3), pp. 1-23

Abstract
Endoluminal vacuum-assisted closure (E-VAC) is a promising therapy to treat anastomotic leakages of the oesophagus and bowel which are associated with high morbidity and mortality rates. An open-pore polyurethane foam is introduced into the leakage cavity and connected to a device that applies a suction pressure to accelerate the closure of the defect. Computational analysis of this healing process can advance our understanding of the biomechanical mechanisms at play. To this aim, we use a dual-stage finite-element analysis in which (i) the structural problem addresses the cavity reduction caused by the suction and (ii) a new constitutive formulation models tissue healing via permanent deformations coupled to a stiffness increase. The numerical implementation in an in-house code is described and a qualitative example illustrates the basic characteristics of the model. The computational model successfully reproduces the generic closure of an anastomotic leakage cavity, supporting the hypothesis that suction pressure promotes healing by means of the aforementioned mechanisms. However, the current framework needs to be enriched with empirical data to help advance device designs and treatment guidelines. Nonetheless, this conceptual study confirms that computational analysis can reproduce E-VAC of anastomotic leakages and establishes the bases for better understanding the mechanobiology of anastomotic defect healing.
Abstract
Endoluminal vacuum-assisted closure (E-VAC) is a promising therapy to treat anastomotic leakages of the oesophagus and bowel which are associated with high morbidity and mortality [...]
- 1
- read
Out-of-equilibrium mechanochemistry and self-organization of fluid membranes interacting with curved proteins
C. Tozzi, N. Walani, M. Arroyo

New journal of physics (2019). Vol. 21, pp. 1-23

Abstract
The function of biological membranes is controlled by the interaction of the fluid lipid bilayer with various proteins, some of which induce or react to curvature. These proteins can preferentially bind or diffuse towards curved regions of the membrane, induce or stabilize membrane curvature and sequester membrane area into protein-rich curved domains. The resulting tight interplay between mechanics and chemistry is thought to control organelle morphogenesis and dynamics, including traffic, membrane mechanotransduction, or membrane area regulation and tension buffering. Despite all these processes are fundamentally dynamical, previous work has largely focused on equilibrium and a self-consistent theoretical treatment of the dynamics of curvature sensing and generation has been lacking. Here, we develop a general theoretical and computational framework based on a nonlinear Onsager’s formalism of irreversible thermodynamics for the dynamics of curved proteins and membranes. We develop variants of the model, one of which accounts for membrane curving by asymmetric crowding of bulky off-membrane protein domains. As illustrated by a selection of test cases, the resulting governing equations and numerical simulations provide a foundation to understand the dynamics of curvature sensing, curvature generation, and more generally membrane curvature mechano-chemistry.
Abstract
The function of biological membranes is controlled by the interaction of the fluid lipid bilayer with various proteins, some of which induce or react to curvature. These proteins [...]
- 1
- read
Modeling human tissues : an efficient integrated methodology
G. Gavidia, E. Soudah, M. Cerrolaza, M. Martín

Biomedical engineering: applications, basis and communications (2014). Vol. 26 (1), pp. 1-21

Abstract
Geometric models of human body organs are obtained from imaging techniques like computed tomography (CT) and magnetic resonance image (MRI) that oallow an accurate visualization of the inner body, thus providing relevant information about their its structure and pathologies. Next, these models are used to generate surface and volumetric meshes, which can be used further for visualization, measurement, biomechanical simulation, rapid prototyping and prosthesis design. However, going from geometric models to numerical models is not an easy task, being necessary to apply image-processing techniques to solve the complexity of human tissues and to get more simplified geometric models, thus reducing the complexity of the subsequent numerical analysis. In this work, an integrated and efficient methodology to obtain models of soft tissues like gray and white matter of brain and hard tissues like jaw and spine bones is proposed. The methodology is based on image-processing algorithms chosen according to some characteristics of the tissue: type, intensity profiles and boundaries quality. First, low-quality images are improved by using enhancement algorithms to reduce image noise and to increase structures contrast. Then, hybrid segmentation for tissue identification is applied through a multi-stage approach. Finally, the obtained models are resampled and exported in formats readable by computer aided design (CAD) tools. In CAD environments, this data is used to generate discrete models using finite element methed (FEM) or other numerical methods like the boundary element method (BEM). Results have shown that the proposed methodology is useful and versatile to obtain accurate geometric models that can be used in several clinical cases to obtain relevant quantitative and qualitative information.
Abstract
Geometric models of human body organs are obtained from imaging techniques like computed tomography (CT) and magnetic resonance image (MRI) that oallow an accurate visualization [...]
- 1
- read
Marchetti flat dilatometer tests in a virtual calibration chamber
J. Butlanska, M. Arroyo, S. Amoroso, A. Gens

Geotechnical Testing Journal (2018). Vol. 41 (5), pp. 1-17 (Preprint)

Abstract
Calibration chambers are frequently used to verify, adapt, or both verify and adapt empirical relations between different state variables and in situ test results. Virtual calibration chambers (VCC) built with 3D discrete element models may be used to extend and partially substitute costly physical testing series. VCC are used here to explore the mechanics of flat dilatometer penetration and expansion. Results obtained for a simulation of physical tests in Ticino sand are presented. Blade tip resistance during penetration is in good agreement with the experiments. A piston-like design is used for the blade so that larger displacements may be applied than it is possible with a membrane. Initial piston pressures in the expansion curves are very low, strongly affected by the scaled-up grain sizes. Despite that difficulty, expansion curves may be easily interpreted to recover dilatometer moduli ED close to those observed in the physical experiments. Particle-scale examination of the results allows a firmer understanding of the current limitations and future potential of the technique. Copyright ASTM International. All rights reserved, 2018/16/07. Downloaded by UPC, pursuant to Author/Copyright Owner Agreement. No further reproduction authorized.
Abstract
Calibration chambers are frequently used to verify, adapt, or both verify and adapt empirical relations between different state variables and in situ test results. Virtual [...]
- 1
- read
Development of a predictive model for rheumatoid arthritis mortality using random survival forest
L. Rodríguez-Rodríguez, J. Lezcano, E. Soudah, J. Jover, I. González-Álvarez, F. Salazar, L. Abásolo

Annals of the Rheumatic Diseases (2017). Vol. 76 (S2), pp. 520

Abstract
Different machine learning methods have been used to develop predictive models of high quality and precision [1]. Among them, Random Survival Forests (RSF) has been proposed as an alternative to traditional survival models [2], being able to overcome most of the limitation of traditional survival techniques, such as Cox proportional hazards models. Objectives Our objective was to develop and internally validate a predictive model for rheumatoid arthritis (RA) mortality using Random Survival Forests (RSF). Methods Retrospective longitudinal study involving 1,461 patients diagnosed with RA between January 1994 and August 2011, and followed at the outpatient clinic of the Rheumatology Department of the Hospital Clínico San Carlos (Madrid, Spain) until death or September 2013. Demographic and clinical-related variables collected during the first two years after disease diagnosis were used. RSF models were developed, based on 1,000 trees. 100 iterations of each model were performed to measure the mean and standard deviation (SD) of the predictive error and the integrated Brier score (IBS). Missing values were imputed using the function implemented by the randomForestSRC package [3]. The predictive capacity of the variables was assessed using the “variable importance” (VIMP). Two models were constructed using the log-rank (MLG) or log-rank score (MLGS) splitting rules. The model with the lowest prediction error was selected. Next, those variables with negative VIMP were excluded and a final model developed. Results 148 patients died (10.1%). MLG showed the lowest prediction error. All variables exhibited a positive VIMP. Final model showed a mean (SD) prediction error and IBS of 0.187 (0.002) and 0.150 (0.003) respectively. The most important predictor variables were age at diagnosis, median erythrocyte sedimentation rate and number of hospital admissions in the first 2 years after RA diagnosis. Conclusions We developed an accurate and precise model for RA mortality using RSF. Age and disease activity showed the highest influence in mortality.
Abstract
Different machine learning methods have been used to develop predictive models of high quality and precision [1]. Among them, Random Survival Forests (RSF) has been [...]
- 1
- read
Diffusion-reaction model for Drosophila embryo development
R. Allena, J. Muñoz, D. Aubry

Comput. Methods Appl. Mech. Engrg., (2011). Vol. 16 (3), pp. 235-248

Abstract
During the early stages of gastrulation in Drosophila embryo, the epithelial cells composing the single tissue layer of the egg undergo large strains and displacements. These movements have been usually modelled by decomposing the total deformation gradient in an (imposed or strain/stress dependent) active part and a passive response. Although the influence of the chemical and genetic activity in the mechanical response of the cell has been experimentally observed, the effects of the mechanical deformation on the latter have been far less studied, and much less modelled. Here, we propose a model that couples morphogen transport and the cell mechanics during embryogenesis. A diffusion-reaction equation is introduced as an additional mechanical regulator of morphogenesis. Consequently, the active deformations are not directly imposed in the analytical formulation, but they rather depend on the morphogen concentration, which is introduced as a new variable. In this study, we show that strain patterns similar to those observed during biological experiments can be reproduced by properly combining the two phenomena. In addition, we use a novel technique to parameterise the embryo geometry by solving two Laplace problems with specific boundary conditions. We apply the method to two morphogenetic movements: ventral furrow invagination and germ band extension. The matching between our results and the observed experimental deformations confirms that diffusion-reaction of morphogens can actually be controlling large morphogenetic movements.
Abstract
During the early stages of gastrulation in Drosophila embryo, the epithelial cells composing the single tissue layer of the egg undergo large strains and displacements. [...]
- 1
- read
Control of cell-cell forces and collective cell dynamics by the intercellular adhesome
E. Bazellières, V. Conte, A. Elosegui-Artola, X. Serra-Picamal, M. Bintanel-Morcillo, P. Roca-Cusachs, J. Muñoz, M. Sales-Pardo, R. Guimerà, X. Trepat

Nature Cell Biology (2015). Vol. 17 (4), pp. 409-420

Abstract
Dynamics of epithelial tissues determine key processes in development, tissue healing and cancer invasion. These processes are critically influenced by cell–cell adhesion forces. However, the identity of the proteins that resist and transmit forces at cell–cell junctions remains unclear, and how these proteins control tissue dynamics is largely unknown. Here we provide a systematic study of the interplay between cell–cell adhesion proteins, intercellular forces and epithelial tissue dynamics. We show that collective cellular responses to selective perturbations of the intercellular adhesome conform to three mechanical phenotypes. These phenotypes are controlled by different molecular modules and characterized by distinct relationships between cellular kinematics and intercellular forces. We show that these forces and their rates can be predicted by the concentrations of cadherins and catenins. Unexpectedly, we identified different mechanical roles for P-cadherin and E-cadherin; whereas P-cadherin predicts levels of intercellular force, E-cadherin predicts the rate at which intercellular force builds up.
Abstract
Dynamics of epithelial tissues determine key processes in development, tissue healing and cancer invasion. These processes are critically influenced by cell–cell [...]
- 1
- read
Computation of forces from deformed visco-elastic biological tissues
J. Muñoz, D. Amat, V. Conte

Inverse Problems (2018). Vol. 34 (4), pp. 1-27 (Preprint)

Abstract
We present a least-squares based inverse analysis of visco-elastic biological tissues. The proposed method computes the set of contractile forces (dipoles) at the cell boundaries that induce the observed and quantified deformations. We show that the computation of these forces requires the regularisation of the problem functional for some load configurations that we study here. The functional measures the error of the dynamic problem being discretised in time with a second-order implicit time-stepping and in space with standard finite elements. We analyse the uniqueness of the inverse problem and estimate the regularisation parameter by means of an L-curved criterion. We apply the methodology to a simple toy problem and to an in vivo set of morphogenetic deformations of the Drosophila embryo.
Abstract
We present a least-squares based inverse analysis of visco-elastic biological tissues. The proposed method computes the set of contractile forces (dipoles) at the cell boundaries [...]
- 1
- read
Mapping forces and kinematics during collective cell migration
X. Serra-Picamal, V. Conte, R. Sunyer, J. Muñoz, X. Trepat

Methods in Cell Biology (2015). Vol. 125, pp. 309-330

Abstract
Fundamental biological processes including morphogenesis and tissue repair require cells to migrate collectively. In these processes, epithelial or endothelial cells move in a cooperative manner coupled by intercellular junctions. Ultimately, the movement of these multicellular systems occurs through the generation of cellular forces, exerted either on the substrate via focal adhesions (cell–substrate forces) or on neighboring cells through cell–cell junctions (cell–cell forces). Quantitative measurements of multicellular forces and kinematics with cellular or subcellular resolution have become possible only in recent years. In this chapter, we describe some of these techniques, which include particle image velocimetry to map cell velocities, traction force microscopy to map forces exerted by cells on the substrate, and monolayer stress microscopy to map forces within and between cells. We also describe experimental protocols to perform these measurements. The combination of these techniques with high-resolution imaging tools and molecular perturbations will lead to a better understanding of the mechanisms underlying collective cell migration in health and disease.
Abstract
Fundamental biological processes including morphogenesis and tissue repair require cells to migrate collectively. In these processes, epithelial or endothelial [...]
- 1
- read
Mechanisms Involved in the Formation of Biocompatible Lipid Polymeric Hollow Patchy Particles
N. Rasheed, A. Khorasani, J. Cebral, C. Salvador-Morales, F. Mut, R. Lohner

Langmuir (2015). Vol. 31 (24), pp. 6639-6648

Abstract
Patchy polymeric particles have anisotropic surface domains that can be remarkably useful in diverse medical and industrial fields because of their ability to simultaneously present two different surface chemistries on the same construct. In this article, we report the mechanisms involved in the formation of novel lipid–polymeric hollow patchy particles during their synthesis. By cross-sectioning the patchy particles, we found that a phase segregation phenomenon occurs between the core, shell, and patch. Importantly, we found that the shear stress that the polymer blend undergoes during the particle synthesis is the most important parameter for the formation of these patchy particles. In addition, we found that the interplay of solvent–solvent, polymer–solvent, and polymer–polymer–solvent interactions generates particles with different surface morphologies. Understanding the mechanisms involved in the formation of patchy particles allows us to have a better control on their physicochemical properties. Therefore, these fundamental studies are critical to achieve batch control and scalability, which are essential aspects that must be addressed in any type of particle synthesis to be safely used in medicine.
Abstract
Patchy polymeric particles have anisotropic surface domains that can be remarkably useful in diverse medical and industrial fields because of their ability to simultaneously [...]
- 1
- read
Computational Hemodynamics Framework for the Analysis of Cerebral Aneurysms
F. Mut, R. Lohner, A. Chien, S. Tateshima, F. Viñuela, C. Putman, J. Cebral

Int. J. Numer. Meth. Bio. Engng. (2010). Vol. 27 (6), pp. 822-839

Abstract
Assessing the risk of rupture of intracranial aneurysms is important for clinicians because the natural rupture risk can be exceeded by the small but significant risk carried by current treatments. To this end numerous investigators have used image‐based computational fluid dynamics models to extract patient‐specific hemodynamics information, but there is no consensus on which variables or hemodynamic characteristics are the most important. This paper describes a computational framework to study and characterize the hemodynamic environment of cerebral aneurysms in order to relate it to clinical events, such as growth or rupture. In particular, a number of hemodynamic quantities are proposed to describe the most salient features of these hemodynamic environments. Application to a patient population indicates that ruptured aneurysms tend to have concentrated inflows, concentrated wall shear stress distributions, high maximal wall shear stress, and smaller viscous dissipation ratios than unruptured aneurysms. Furthermore, these statistical associations are largely unaffected by the choice of physiologic flow conditions. This confirms the notion that hemodynamic information derived from image‐based computational models can be used to assess aneurysm rupture risk, to test hypotheses about the mechanisms responsible for aneurysm formation, progression, and rupture, and to answer specific clinical questions.
Abstract
Assessing the risk of rupture of intracranial aneurysms is important for clinicians because the natural rupture risk can be exceeded by the small but significant risk carried [...]
- 1
- read
Hemodynamic Analysis of Intracranial Aneurysms with Moving Parent Arteries: Basilar Tip Aneurysms
D. Sforza, R. Lohner, C. Putman, J. Cebral

Int. J. Numer. Meth. Bio. Engng. (2010). Vol. 26 (10), pp. 1219-1227

Abstract
The effects of parent artery motion on the hemodynamics of basilar tip saccular aneurysms and its potential effect on aneurysm rupture were studied. The aneurysm and parent artery motions in two patients were determined from cine loops of dynamic angiographies. The oscillatory motion amplitude was quantified by registering the frames. Patient‐specific computational fluid dynamics (CFD) models of both aneurysms were constructed from 3D rotational angiography images. Two CFD calculations were performed for each patient, corresponding to static and moving models. The motion estimated from the dynamic images was used to move the surface grid points in the moving model. Visualizations from the simulations were compared for wall shear stress (WSS), velocity profiles, and streamlines. In both patients, a rigid oscillation of the aneurysm and basilar artery in the anterio‐posterior direction was observed and measured. The distribution of WSS was nearly identical between the models of each patient, as well as major intra‐aneurysmal flow structures, inflow jets, and regions of impingement. The motion observed in pulsating intracranial vasculature does not have a major impact on intra‐aneurysmal hemodynamic variables. Parent artery motion is unlikely to be a risk factor for increased risk of aneurysmal rupture.
Abstract
The effects of parent artery motion on the hemodynamics of basilar tip saccular aneurysms and its potential effect on aneurysm rupture were studied. The aneurysm and parent [...]
- 1
- read
The journal Communications in Numerical Methods in Engineering with Biomedical Applications becomes the International Journal for Numerical Methods in Biomedical Engineering (IJNMBE) from 1st January 2010
P. Nithiarasu, R. Lohner

Int. J. Numer. Meth. Fluids (2009). Vol. 61 (10), pp. 1179-1180

Abstract
Communications in Numerical Methods in Engineering , founded by Roland W. Lewis in 1985, will change its title to the ‘International Journal for Numerical Methods in Biomedical Engineering ’ and has a revised Aims and Scope.
Abstract
Communications in Numerical Methods in Engineering , founded by Roland W. Lewis in 1985, will change its title to the ‘International Journal for Numerical Methods [...]
- 1
- read
Fast numerical solutions of patient‐specific blood flows in 3D arterial systems
F. Mut, R. Aubry, R. Lohner, J. Cebral

Int. J. Numer. Meth. Bio. Engng. (2010). Vol. 26 (1), pp. 73-86

Abstract
The study of hemodynamics in arterial models constructed from patient‐specific medical images requires the solution of the incompressible flow equations in geometries characterized by complex branching tubular structures. The main challenge with this kind of geometries is that the convergence rate of the pressure Poisson solver is dominated by the graph depth of the computational grid. This paper presents a deflated preconditioned conjugate gradients (DPCG) algorithm for accelerating the pressure Poisson solver. A subspace deflation technique is used to approximate the lowest eigenvalues along the tubular domains. This methodology was tested with an idealized cylindrical model and three patient‐specific models of cerebral arteries and aneurysms constructed from medical images. For these cases, the number of iterations decreased by up to a factor of 16, while the total CPU time was reduced by up to 4 times when compared with the standard PCG solver.
Abstract
The study of hemodynamics in arterial models constructed from patient‐specific medical images requires the solution of the incompressible flow equations in geometries characterized [...]
- 1
- read
Blood-flow models of the circle of Willis from magnetic resonance data
J. Cebral, M. Castro, O. Soto, R. Lohner, N. Alperin

Journal of Engineering Mathematics (2003). Vol. 47, pp. 369-386

Abstract
Detailed knowledge of the cerebral hemodynamics is important for a variety of clinical applications. Cerebral perfusion depends not only on the status of the diseased vessels but also on the patency of collateral pathways provided by the circle of Willis. Due to the large anatomical and physiologic variability among individuals, realistic patient-specific models can provide new insights into the cerebral hemodynamics. This paper presents an image-based methodology for constructing patient-specific models of the cerebral circulation. This methodology combines anatomical and physiologic imaging techniques with computer simulation technology. The methodology is illustrated with a finite element model constructed from magnetic resonance image data of a normal volunteer. Several of the remaining challenging problems are identified. This work represents a starting point in the development of realistic models that can be applied to the study of cerebrovascular diseases and their treatment.
Abstract
Detailed knowledge of the cerebral hemodynamics is important for a variety of clinical applications. Cerebral perfusion depends not only on the status of the diseased vessels [...]
- 1
- read
From medical images to anatomically accurate finite element grids
J. Cebral, R. Lohner

Int. J. Numer. Meth. Engng. (2001). Vol. 51 (8), pp. 985-1008
- 1
- read
Mechanical oscillations in biological tissues as a result of delayed rest-length changes
J. Muñoz, M. Dingle, M. Wenzel

Physical review E: statistical, nonlinear and soft matter physics (2018). Vol. 98 (5), pp. 1-15 (Preprint)

Abstract
Oscillatory behavior in tissue biology is ubiquitous and may be observed in the form of either chemical or mechanical signals. We present here and solve a mechanical cell model that exhibits oscillations emerging from delayed viscoelastic rheological laws. These include a time delay between the mechanical response and the rest-length changes, which evolve proportionally to the delayed cell deformation and use a remodeling rate parameter. We show that different regimes (no oscillatory response, sustained oscillations, and unstable oscillations) are obtained for different values of the delay or the remodeling rate. The results are analytically demonstrated in a one-dimensional problem with one and two cells that are represented by simple line elements. Oscillations of the cell deformations are obtained whenever different delays coexist, or when the delay is size-dependent. We also extend our results to a multicellular two-dimensional vertex model that includes the same rheological law, and which inherits the presence of critical values of the delay or remodeling rate. We numerically show that indeed the size-dependent rest-length changes induce oscillations in the cell shapes and areas.
Abstract
Oscillatory behavior in tissue biology is ubiquitous and may be observed in the form of either chemical or mechanical signals. We present here and solve a mechanical cell [...]
- 0
- read
A truss element for modelling reversible softening in living tissues
J. Muñoz, V. Conte, N. Asadipour, M. Miodownik

Mechanics Research Communications (2013). Vol. 49, pp. 44-49 (Preprint)

Abstract
We resort to non-linear viscoelasticity to develop a truss element able to model reversible softening in lung epithelial tissues undergoing transient stretch. Such a Maxwell truss element is built by resorting to a three-noded element whose mid-node is kinematically constrained to remain on the line connecting the end-nodes. The whole mechanical system undergoes an additive decomposition of the strains along the truss direction where the total contribution of the mid-node is accounted for by using a null-space projection and static condensation techniques. Assembling of such line-elements in 3D networks allows us to model extended regions of living tissues as well as their anisotropies.
Abstract
We resort to non-linear viscoelasticity to develop a truss element able to model reversible softening in lung epithelial tissues undergoing transient stretch. Such a Maxwell [...]
- 0
- read
A deformation gradient decomposition method for the analysis of the mechanics of morphogenesis
J. Muñoz, K. Barrett, M. Miodownik

Journal of Biomechanics (2007). Vol. 40 (6), pp. 1372-1380

Abstract
A new finite element model is proposed for the analysis of the mechanical aspects of morphogenesis and tested on the biologically well studied gastrulation phenomenon, in particular ventral furrow invagination of the Drosophila melanogaster embryo. A set of mechanisms are introduced in the numerical model, which lead to the observed deformed shapes. We split the total deformation into two parts: an imposed active deformation, and an elastic deformation superimposed onto the latter. The active deformation simulates the effects of apical constriction and apico-basal elongation. These mechanisms are associated with known gene expressions and so in this way we attempt to bridge the well explored signalling pathways, and their associated phenotypes in a mechanical model. While the former have been studied in depth, much less can be said about the forces they produce and the mechanisms involved. From the numerical results, we are able to test different plausible mechanical hypotheses that generate the necessary folding observed in the invagination process. In particular, we conclude that only certain ratios between both modes (apical constriction and apico-basal elongation) can successfully reproduce the invagination process. The model also supports the idea that this invagination requires the contribution of several mechanisms, and that their redundancy provides the necessary robustness.
Abstract
A new finite element model is proposed for the analysis of the mechanical aspects of morphogenesis and tested on the biologically well studied gastrulation phenomenon, in [...]
- 0
- read

information

About this publication

How to submit

Open access

Contact