Dataset Information

A computational study of stress fiber-focal adhesion dynamics governing cell contractility.

ABSTRACT: We apply a recently developed model of cytoskeletal force generation to study a cell's intrinsic contractility, as well as its response to external loading. The model is based on a nonequilibrium thermodynamic treatment of the mechanochemistry governing force in the stress fiber-focal adhesion system. Our computational study suggests that the mechanical coupling between the stress fibers and focal adhesions leads to a complex, dynamic, mechanochemical response. We collect the results in response maps whose regimes are distinguished by the initial geometry of the stress fiber-focal adhesion system, and by the external load on the cell. The results from our model connect qualitatively with recent studies on the force response of smooth muscle cells on arrays of polymeric microposts.

SUBMITTER: Maraldi M

PROVIDER: S-EPMC4017287 | biostudies-other | 2014 May

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

A computational study of stress fiber-focal adhesion dynamics governing cell contractility.

Maraldi M M Valero C C Garikipati K K

Biophysical journal 20140501 9

We apply a recently developed model of cytoskeletal force generation to study a cell's intrinsic contractility, as well as its response to external loading. The model is based on a nonequilibrium thermodynamic treatment of the mechanochemistry governing force in the stress fiber-focal adhesion system. Our computational study suggests that the mechanical coupling between the stress fibers and focal adhesions leads to a complex, dynamic, mechanochemical response. We collect the results in response ...[more]

PMID: 24806921

Similar Datasets

Project description:Cells interact with the extracellular matrix (ECM) via cell-ECM adhesions. These physical interactions are transduced into biochemical signals inside the cell which influence cell behaviour. Although cell-ECM interactions have been studied extensively, it is not completely understood how immature (nascent) adhesions develop into mature (focal) adhesions and how mechanical forces influence this process. Given the small size, dynamic nature and short lifetimes of nascent adhesions, studying them using conventional microscopic and experimental techniques is challenging. Computational modelling provides a valuable resource for simulating and exploring various "what if?" scenarios in silico and identifying key molecular components and mechanisms for further investigation. Here, we present a simplified mechano-chemical model based on ordinary differential equations with three major proteins involved in adhesions: integrins, talin and vinculin. Additionally, we incorporate a hypothetical signal molecule that influences adhesion (dis)assembly rates. We find that assembly and disassembly rates need to vary dynamically to limit maturation of nascent adhesions. The model predicts biphasic variation of actin retrograde velocity and maturation fraction with substrate stiffness, with maturation fractions between 18-35%, optimal stiffness of ∼1 pN/nm, and a mechanosensitive range of 1-100 pN/nm, all corresponding to key experimental findings. Sensitivity analyses show robustness of outcomes to small changes in parameter values, allowing model tuning to reflect specific cell types and signaling cascades. The model proposes that signal-dependent disassembly rate variations play an underappreciated role in maturation fraction regulation, which should be investigated further. We also provide predictions on the changes in traction force generation under increased/decreased vinculin concentrations, complementing previous vinculin overexpression/knockout experiments in different cell types. In summary, this work proposes a model framework to robustly simulate the mechanochemical processes underlying adhesion maturation and maintenance, thereby enhancing our fundamental knowledge of cell-ECM interactions.

Dataset Information

A computational study of stress fiber-focal adhesion dynamics governing cell contractility.

Publications

A computational study of stress fiber-focal adhesion dynamics governing cell contractility.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets