Hysteresis in the cell response to time-dependent substrate stiffness

TL;DR

This paper presents a mechano-chemical model predicting how cells respond to changing substrate stiffness, revealing hysteresis effects and bistable contractility states influenced by mechanical cues.

Contribution

The study introduces a combined mechanical and biochemical model to predict cellular responses to dynamic substrate stiffness, highlighting hysteresis and bistability in cell contractility.

Findings

Bistable cellular contractility as a function of substrate stiffness

Hysteresis in cellular traction forces under time-dependent stiffness

Identification of stiffness thresholds for cell contractile states

Abstract

Mechanical cues like the rigidity of the substrate are main determinants for the decision making of adherent cells. Here we use a mechano-chemical model to predict the cellular response to varying substrate stiffness. The model equations combine the mechanics of contractile actin filament bundles with a model for the Rho-signaling pathway triggered by forces at cell-matrix contacts. A bifurcation analysis of cellular contractility as a function of substrate stiffness reveals a bistable response, thus defining a lower threshold of stiffness, below which cells are not able to build up contractile forces, and an upper threshold of stiffness, above which cells are always in a strongly contracted state. Using the full dynamical model, we predict that rate-dependent hysteresis will occur in the cellular traction forces when cells are exposed to substrates of time-dependent stiffness.