Twofold Mechanosensitivity Ensures Actin Cortex Reinforcement upon Peaks in Mechanical Tension

Abstract

AbstractThe actin cortex is an active polymer network underneath the plasma membrane at the periphery of mammalian cells. It is a major regulator of cell shape through the generation of active cortical tension. In addition, the cortex constitutes a mechanical shield that protects the cell during mechanical agitation. Cortical mechanics is tightly controlled by the presence of actin cross‐linking proteins that dynamically bind and unbind actin filaments. Cross‐linker actin bonds are weak non‐covalent bonds whose bond lifetime is likely affected by mechanical tension in the actin cortex making cortical composition inherently mechanosensitive. Here, a quantitative study of changes in cortex composition and turnover dynamics upon short‐lived peaks in active and passive mechanical tension in mitotic HeLa cells is presented. These findings dsclose a twofold mechanical reinforcement strategy of the cortex upon tension peaks entailing i) a direct catch‐bond mechanosensitivity of cross‐linkers filamin and α‐actinin and ii) an indirect cortical mechanosensitivity that triggers actin cortex reinforcement via enhanced polymerization of actin. Thereby a “molecular safety belt” mechanism that protects the cortex from injury upon mechanical challenges is disclosed.