The Molecular Landscape of Mechanosensing by the Cell Cortex

Abstract

Mechanical forces direct a host of cellular and tissue processes. While much emphasis is placed on cell adhesion complexes as force sensors, these forces must be transmitted through the cortical cytoskeleton. However, how the cortex senses and transmits forces and how cytoskeletal proteins interact in response to these forces are poorly understood. Here, by combining molecular and mechanical experimental perturbations with theoretical multi-scale modeling, we decipher cortical mechanosensing from molecular to cellular scales. Forces are shared between myosin II and different actin crosslinkers with myosin having potentiating or inhibitory effects on certain crosslinkers. Furthermore, different types of cell deformations elicit distinct responses: myosin and α-actinin respond to dilation while filamin mainly reacts to shear. The kinetics of each protein's accumulation may be explained by its molecular mechanisms. Finally, protein accumulation, along with the cell's viscoelastic state, can also explain the monotonic or oscillatory contraction against mechanical load in different mutant strains.