Dynamics of focal adhesion orientation in response to time varying stretch

Mechanical forces play a central role in determining cell function and fate. The effect of time varying stretch is particularly striking which affects many cellular processes such as adhesion, orientation, migration, wound healing to name a few. Focal adhesions act as mechanosensors and in turn regulate the response of cells in tissues. It is not yet well understood how the stretch induces cytoskeletal organization, or how it affects the assembly of focal adhesions. We present a simple theoretical model based on 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 cyclic stretches. Our 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. Moreover, it also elucidates the existence of threshold frequency and stretch magnitude for orientational response that have been found to vary across cell types.
1. R. De, Communications Biology, Vol. 1 (81) 2018.