A general model of focal adhesion orientation dynamics in response to static and cyclic stretch

Abstract

Understanding cellular response to mechanical forces is immensely important for a plethora of biological processes. Focal adhesions are multimolecular protein assemblies that connect the cell to the extracellular matrix and play a pivotal role in cell mechanosensing. Under time-varying stretches, focal adhesions dynamically reorganize and reorient and as a result, regulate the response of cells in tissues. Here I present a simple theoretical model based on, to my knowledge, a novel approach in the understanding of stretch-sensitive bond association and dissociation processes together with the elasticity of the cell-substrate system to predict the growth, stability, and the orientation of focal adhesions in the presence of static as well as cyclically varying stretches. The model agrees well with several experimental observations; most importantly, it explains the puzzling observations of parallel orientation of focal adhesions under static stretch and nearly perpendicular orientation in response to fast varying cyclic stretch.