Mathematical Modelling of Mechanotransduction via RhoA Signalling Pathways

TL;DR

This paper develops a mathematical model combining RhoA signalling pathways with cell mechanics, revealing how cell shape and substrate stiffness influence mechanotransduction and cell stability.

Contribution

It introduces a coupled reaction-diffusion and elasticity model with a novel numerical method for simulating cell mechanotransduction processes.

Findings

Cell shape significantly affects signalling dynamics.

A threshold response to substrate stiffness was observed.

Coupling mechanics and signalling enhances cell deformation robustness.

Abstract

We derive and simulate a mathematical model for mechanotransduction related to the Rho GTPase signalling pathway. The model addresses the bidirectional coupling between signalling processes and cell mechanics. A numerical method based on bulk-surface finite elements is proposed for the approximation of the coupled system of nonlinear reaction-diffusion equations, defined inside the cell and on the cell membrane, and the equations of elasticity. Our simulation results illustrate novel emergent features such as the strong dependence of the dynamics on cell shape, a threshold-like response to changes in substrate stiffness, and the fact that coupling mechanics and signalling can lead to the robustness of cell deformation to larger changes in substrate stiffness, ensuring mechanical homeostasis in agreement with experiments.