Role of catch bonds in actomyosin mechanics and cell mechanosensitivity

Vernerey, Franck J.; Akalp, Umut

doi:10.1103/physreve.94.012403

Cited by 26 publications

(35 citation statements)

References 62 publications

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“…It is therefore evident that to uncover the biomechanisms underlying such observations, a statistical mechanics approach to cell modeling is required. Typically, previous models have assumed the spread state as the reference configuration and simulate a single deterministic outcome (6)(7)(8)(9)(10)(11)(12). McEvoy et al (13) recently implemented a framework whereby an initially unadhered cell deforms to a range of possible spread states, and the system free energy is computed for each configuration.…”

Section: Introductionmentioning

confidence: 99%

Thermodynamic Modeling of the Statistics of Cell Spreading on Ligand-Coated Elastic Substrates

McEvoy

Shishvan

Deshpande

et al. 2018

Biophysical Journal

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Biological spread cells exist in a perpetually fluctuating state and therefore cannot be described in terms of a unique deterministic system. For modeling approaches to provide novel insight and uncover new mechanisms that drive cell behavior, a framework is required that progresses from traditional deterministic methods (whereby simulation of an experiment predicts a single outcome). In this study, we implement a new, to our knowledge, modeling approach for the analysis of cell spreading on ligand-coated substrates, extending the framework for nonequilibrium thermodynamics of cells developed by Shishvan et al. to include active focal adhesion assembly. We demonstrate that the model correctly predicts the coupled influence of surface collagen density and substrate stiffness on cell spreading, as reported experimentally by Engler et al. Low surface collagen densities are shown to result in a high probability that cells will be restricted to low spread areas. Furthermore, elastic free energy induced by substrate deformation lowers the probability of observing a highly spread cell, and, consequentially, lower cell tractions affect the assembly of focal adhesions. Experimentally measurable observables such as cell spread area and aspect ratio can be directly postprocessed from the computed homeostatic ensemble of (several million) spread states. This allows for the prediction of mean and SDs of such experimental observables. This class of cell mechanics modeling presents a significant advance on conventional deterministic approaches.

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Section: Introductionmentioning

confidence: 99%

Thermodynamic Modeling of the Statistics of Cell Spreading on Ligand-Coated Elastic Substrates

McEvoy

Shishvan

Deshpande

et al. 2018

Biophysical Journal

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“…The final governing equations were derived by ensuring that active, dissipative, and elastic forces are balanced. This final step was confirmed when the functional ℱ SF is minimized, 7 i.e.,

\partial {\dot{δ}}_{e} {false(ℱ_{SF} false)}_{, {\dot{δ}}_{e}} + \partial \dot{η} {false(ℱ_{SF} false)}_{, \dot{η}} + \partial ν_{s} {false(ℱ_{SF} false)}_{, ν_{s}} = 0

where the subscripts are used to denote differential operators. Assuming that the variables η̇ , δ̇ e , and v s are independent of each other, the three terms in eq 10 must be minimized separately, which leads three Euler–Lagrange equations.…”

Section: Methodsmentioning

confidence: 74%

“…The distributed transverse load q ( x , t ) and axial load p ( x , t ) further arise from the contraction of stress fiber attached to the cortex. 7 The flexural stiffness E c I c was chosen to be 1.42 × 10 −9 dyn·cm, consistent with experimental observations. 35,36 …”

Section: Methodsmentioning

confidence: 99%

Structural Modeling of Mechanosensitivity in Non-Muscle Cells: Multiscale Approach to Understand Cell Sensing

Akalp

Schnatwinkel

Stoykovich

et al. 2017

ACS Biomater. Sci. Eng.

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The contraction and spreading of nonmuscle cells are important phenomena in a number of cellular processes such as differentiation, morphogenesis, and tissue growth. Recent experimental work has shown that the topology and the mechanical properties of the underlying substrate play a significant role in directing the cell’s response. In this work, we introduce a multiscale model to understand the sensing, activation, and contraction of the actin cytoskeleton of nonmuscle cells based on the idea that acto-myosin cross-bridges display a catch-bond response. After investigating the respective roles of bond catchiness and acto-myosin assembly on the mechano-sensitivity of stress fibers, we present full simulations of cells laying on arrays of micropillars. Model predictions show good qualitative agreements with experimental observation, suggesting that acto-myosin catch bonds are a major mechano-sensing element in nonmuscle cells.

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“…The differentiation of these cells to the appropriate type depends on bio-chemical and mechanical cues 57 that can be provided by the hydrogels. In this context, computational models of cell mechano-sensitivity 58–61 based on mixture theories 62 , transport and mechanics of interfaces 63–65 or structural models 66,67 can be used to understand the role of gel properties on differentiation. Such approaches can be combined with the gel degradation-tissue growth model proposed in this article to tune hydrogel design that induces appropriate cell differentiation and subsequent tissue growth.…”

Section: Summary and Final Remarksmentioning

confidence: 99%

Heterogeneity is key to hydrogel-based cartilage tissue regeneration

et al. 2017

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Degradable hydrogels have been developed to provide initial mechanical support to encapsulated cells while facilitating growth of neo-tissues. When cells are encapsulated within degradable hydrogels, the process of neo-tissue growth is complicated by the coupled phenomena of transport of large extracellular matrix macromolecules and the rate of hydrogel degradation. If hydrogel degradation is too slow, neo-tissue growth is hindered, whereas if it is too fast, complete loss of mechanical integrity can occur. Therefore, there is a need for effective modelling techniques to predict hydrogel designs based on the growth parameters of the neo-tissue. In this article, hydrolytically degradable hydrogels are investigated due to their promise in tissue engineering. A key output of the model focuses on the ability of the construct to maintain overall structural integrity as the construct transitions from pure hydrogel to an engineered neo-tissue. We show that heterogeneity in cross-link density and cell distribution are key elements for this successful transition and ultimately to achieve tissue growth. Specifically, we find that optimally large regions of weak cross-linking around cells in the hydrogel and well-connected and dense cell clusters create the optimum conditions needed for neo-tissue growth while maintaining structural integrity. Experimental observations using cartilage cells encapsulated in a hydrolytically degradable hydrogel are compared with model predictions to show the potential of the proposed model.

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Role of catch bonds in actomyosin mechanics and cell mechanosensitivity

Cited by 26 publications

References 62 publications

Thermodynamic Modeling of the Statistics of Cell Spreading on Ligand-Coated Elastic Substrates

Thermodynamic Modeling of the Statistics of Cell Spreading on Ligand-Coated Elastic Substrates

Structural Modeling of Mechanosensitivity in Non-Muscle Cells: Multiscale Approach to Understand Cell Sensing

Heterogeneity is key to hydrogel-based cartilage tissue regeneration

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