Single-cell response to stiffness exhibits muscle-like behavior

Mitrossilis, Démosthène; Fouchard, Jonathan; Guiroy, Axel; Desprat, Nicolas; Rodriguez, Nicolas; Fabry, Ben; Asnacios, Atef

doi:10.1073/pnas.0903994106

Cited by 211 publications

(304 citation statements)

References 41 publications

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“…Contractile cells such as fibroblasts, myoblasts, and platelets have been shown to individually generate contractile forces ranging from 0.1 to 300 nN/cell (1,18,37,38). The accumulation of force generated by these individual active contractile cells results in a macroscopic contraction of the matrix.…”

Section: Discussionmentioning

confidence: 99%

“…Recent experiments showed that contractile cells (e.g., fibroblasts) subjected to uniaxial loading have an active stress versus strain-rate response that obeys the classic Hill relation (18,28). As in other contractile cells, contraction in platelets involves myosin-actin interactions (29).…”

Section: Properties Of Constitutive Componentsmentioning

confidence: 99%

“…Single contractile cells such as platelets display a force-velocity relationship that is well characterized by the Hill equation due to the conservation of the kinetics of clot contraction across different cell types (16)(17)(18). Fibrin is a nonlinear viscoelastic material that can be modeled using a Kelvin-Voigt model (19).…”

Section: Introductionmentioning

confidence: 99%

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Interplay of Platelet Contractility and Elasticity of Fibrin/Erythrocytes in Blood Clot Retraction

Tutwiler

Wang

Litvinov

et al. 2017

Biophysical Journal

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Blood clot contraction (retraction) is driven by platelet-generated forces propagated by the fibrin network and results in clot shrinkage and deformation of erythrocytes. To elucidate the mechanical nature of this process, we developed a model that combines an active contractile motor element with passive viscoelastic elements. Despite its importance for thrombosis and wound healing, clot contraction is poorly understood. This model predicts how clot contraction occurs due to active contractile platelets interacting with a viscoelastic material, rather than to the poroelastic nature of fibrin, and explains the observed dynamics of clot size, ultrastructure, and measured forces. Mechanically passive erythrocytes and fibrin are present in series and parallel to active contractile cells. This mechanical interplay induces compressive and tensile resistance, resulting in increased contractile force and a reduced extent of contraction in the presence of erythrocytes. This experimentally validated model provides the fundamental mechanical basis for understanding contraction of blood clots.

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Section: Discussionmentioning

confidence: 99%

Section: Properties Of Constitutive Componentsmentioning

confidence: 99%

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Interplay of Platelet Contractility and Elasticity of Fibrin/Erythrocytes in Blood Clot Retraction

Tutwiler

Wang

Litvinov

et al. 2017

Biophysical Journal

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“…2 a) and a stiffer endothelium also impedes transmigration. Although the modulus of the ECM ðm t Þ has little influence on the resistance force, it has a strong effect on the actomyosin contractile forces: at the same chemomechanical coupling level, a softer ECM induces lower levels of cellular contractile force (21,26,27), which may not be sufficient for the cells to overcome the resistance force. Therefore, it is less likely for the cell to transmigrate when the ECM is soft (Fig.…”

Section: Ecm Stiffness and Gap Size Modulate Nuclear Transmigrationmentioning

confidence: 99%

A Chemomechanical Model for Nuclear Morphology and Stresses during Cell Transendothelial Migration

Cao

Moeendarbary

Isermann

et al. 2016

Biophysical Journal

119

160

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It is now evident that the cell nucleus undergoes dramatic shape changes during important cellular processes such as cell transmigration through extracellular matrix and endothelium. Recent experimental data suggest that during cell transmigration the deformability of the nucleus could be a limiting factor, and the morphological and structural alterations that the nucleus encounters can perturb genomic organization that in turn influences cellular behavior. Despite its importance, a biophysical model that connects the experimentally observed nuclear morphological changes to the underlying biophysical factors during transmigration through small constrictions is still lacking. Here, we developed a universal chemomechanical model that describes nuclear strains and shapes and predicts thresholds for the rupture of the nuclear envelope and for nuclear plastic deformation during transmigration through small constrictions. The model includes actin contraction and cytosolic back pressure that squeeze the nucleus through constrictions and overcome the mechanical resistance from deformation of the nucleus and the constrictions. The nucleus is treated as an elastic shell encompassing a poroelastic material representing the nuclear envelope and inner nucleoplasm, respectively. Tuning the chemomechanical parameters of different components such as cell contractility and nuclear and matrix stiffnesses, our model predicts the lower bounds of constriction size for successful transmigration. Furthermore, treating the chromatin as a plastic material, our model faithfully reproduced the experimentally observed irreversible nuclear deformations after transmigration in lamin-A/C-deficient cells, whereas the wild-type cells show much less plastic deformation. Along with making testable predictions, which are in accord with our experiments and existing literature, our work provides a realistic framework to assess the biophysical modulators of nuclear deformation during cell transmigration.

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“…A number of cells such as fibroblasts, cardiomyocytes, epithelial cells, endothelial cells and smooth muscle cells develop significant contractile forces as part of their physiological function [9][10][11][12]. One important function of cellular forces is to act on the surrounding extracellular matrix (ECM), align the matrix and reorganize tissues as they form and develop.…”

Section: Introductionmentioning

confidence: 99%

A chemo-mechanical free-energy-based approach to model durotaxis and extracellular stiffness-dependent contraction and polarization of cells

Shenoy¹,

Wang²,

Xiao³

2016

Interface Focus.

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We propose a chemo-mechanical model based on stress-dependent recruitment of myosin motors to describe how the contractility, polarization and strain in cells vary with the stiffness of their surroundings and their shape. A contractility tensor, which depends on the distribution of myosin motors, is introduced to describe the chemical free energy of the cell due to myosin recruitment. We explicitly include the contributions to the free energy that arise from mechanosensitive signalling pathways (such as the SFX, Rho-Rock and MLCK pathways) through chemo-mechanical coupling parameters. Taking the variations of the total free energy, which consists of the chemical and mechanical components, in accordance with the second law of thermodynamics provides equations for the temporal evolution of the active stress and the contractility tensor. Following this approach, we are able to recover the well-known Hill relation for active stresses, based on the fundamental principles of irreversible thermodynamics rather than phenomenology. We have numerically implemented our free energy-based approach to model spatial distribution of strain and contractility in (i) cells supported by flexible microposts, (ii) cells on two-dimensional substrates, and (iii) cells in three-dimensional matrices. We demonstrate how the polarization of the cells and the orientation of stress fibres can be deduced from the eigenvalues and eigenvectors of the contractility tensor. Our calculations suggest that the chemical free energy of the cell decreases with the stiffness of the extracellular environment as the cytoskeleton polarizes in response to stress-dependent recruitment of molecular motors. The mechanical energy, which includes the strain energy and motor potential energy, however, increases with stiffness, but the overall energy is lower for cells in stiffer environments. This provides a thermodynamic basis for durotaxis, whereby cells preferentially migrate towards stiffer regions of the extracellular environment. Our models also explain, from an energetic perspective, why the shape of the cells can change in response to stiffness of the surroundings. The effect of the stiffness of the nucleus on its shape and the orientation of the stress fibres is also studied for all the above geometries. Along with making testable predictions, we have estimated the magnitudes of the chemo-mechanical coupling parameters for myofibroblasts based on data reported in the literature.

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Single-cell response to stiffness exhibits muscle-like behavior

Cited by 211 publications

References 41 publications

Interplay of Platelet Contractility and Elasticity of Fibrin/Erythrocytes in Blood Clot Retraction

Interplay of Platelet Contractility and Elasticity of Fibrin/Erythrocytes in Blood Clot Retraction

A Chemomechanical Model for Nuclear Morphology and Stresses during Cell Transendothelial Migration

A chemo-mechanical free-energy-based approach to model durotaxis and extracellular stiffness-dependent contraction and polarization of cells

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