A mechanosensing mechanism mediated by IRSp53 controls plasma membrane shape homeostasis at the nanoscale

Abstract

As cells migrate and experience forces from their surroundings, they constantly undergo mechanical deformations which reshape their plasma membrane (PM). To maintain homeostasis, cells need to detect and restore such changes, not only in terms of overall PM area and tension as previously described, but also in terms of local, nano-scale topography. Here we describe a novel phenomenon, by which cells sense and restore mechanically induced PM nano-scale deformations. We show that cell stretch and subsequent compression reshape the PM in a way that generates local membrane evaginations in the 100 nm scale. These evaginations are recognized by the I-BAR protein IRSp53, which triggers a burst of actin polymerization mediated by Rac1 and Arp2/3. The actin polymerization burst subsequently re-flattens the evagination, completing the mechanochemical feedback loop. Our results demonstrate a new mechanosensing mechanism for PM shape homeostasis, with potential applicability in different physiological scenarios.

Cell intrinsic mechanical regulation of plasma membrane accumulation at the cytokinetic furrow

“…This prediction agrees with experimental results in early cytokinesis (20,41). The force-induced plasma membrane deformations revealed by our study could also result in localized regulation of mechanotransduction in cytokinesis (35,42). For example, the membrane accumulation at the intercellular bridge could influence the mechanosensitive Piezo1 channel, which localizes to the intercellular bridge and controls cytokinetic abscission (43).…”

Constant surface area-to-volume ratio during cell growth as a design principle in mammalian cells

“…Curiously, increases in membrane folding are also observed on larger nuclei 63 , suggesting that nuclear deformation could also be size independent. In addition, the size-dependent plasma membrane morphology may result in cell size-dependent mechanosensing, endocytosis and exocytosis, all of which can be impacted by local membrane geometry and/or tension 21,61,[64][65][66][67] .…”

“…We have identified specific cell surface proteins that do not follow isometric size scaling making these proteins potential cell size-sensors. Furthermore, proteins that sense plasma membrane curvature, such as I-BAR proteins and tetraspanins 20,59,60 , could also act as cell size-sensors, because the constant SA/V ratio requires that the plasma membrane accumulates more folding as cell size increases.…”