Plasma membrane mechanosensing upon stretch-induced topography remodelling

Abstract

As cells migrate and experience forces from their surroundings, they constantly undergo mechanical deformations which reshape the plasma membrane. To maintain homeostasis, cells need to detect and restore such changes in plasma membrane shape, but the associated mechanochemical feedback mechanisms are not fully understood. This thesis describes a novel phenomenon, by which cells sense and restore local mechanically induced membrane deformations. The results here presented show that cell stretch, and subsequent release triggers the formation of local membrane evaginations in the 100 nm scale, as observed both by scanning and transmission electron microscopy. These evaginations are then recognized by the I-BAR protein IRSp53, which triggers a burst of actin polymerization via Rac1 and Arp2/3. Actin polymerization subsequently re-flattens the evagination, completing the mechanochemical feedback loop. Mathematical modelling of the Arp2/3 generated network reveals that local enrichment of an actin polymerising species drove by IRSp53 recruitment at the evaginations, generates a gradient in tension that favours in plane forces. This results in a flow that drag the membrane out and flattens the evagination. The results presented in this thesis demonstrate a new mechanosensing mechanism enabling plasma membrane shape homeostasis, with potential applicability in different physiological scenarios.