Extent of myosin penetration within the actin cortex regulates cell surface mechanics

Abstract

In animal cells, shape is mostly determined by the actomyosin cortex, a thin cytoskeletal network underlying the plasma membrane. Myosin motors generate tension in the cortex, and tension gradients result in cellular deformations. As such, many cell morphogenesis studies have focused on the mechanisms controlling myosin activity and recruitment to the cortex. Here, we demonstrate using super-resolution microscopy that myosin does not always overlap with actin at the cortex, but remains restricted towards the cytoplasm in cells with low cortex tension. We propose that this restricted penetration results from steric hindrance, as myosin minifilaments are considerably larger than the cortical actin meshsize. We identify myosin activity and actin network architecture as key regulators of myosin penetration into the cortex, and show that increasing myosin penetration increases cortical tension. Our study reveals that the spatial coordination of myosin and actin at the cortex regulates cell surface mechanics, and unveils an important mechanism whereby myosin size controls its action by limiting minifilament penetration into the cortical actin network. More generally, our findings suggest that protein size could regulate function in dense cytoskeletal structures.

Myosin-dependent partitioning of junctional Prickle2 toward the anterior vertex during planar polarization of Xenopus neuroectoderm

“…Indeed, two recent studies suggest junctional heterogeneity reflects fluctuations of c-cadherin activity along mesenchymal cell-cell contacts (Huebner et al, 2021) as well as NMII-mediated contractility along the adherens junctions (Yang et al, 2022). Recent findings suggest NMII position within the cell cortex, either near to or more distant from the plasma membrane regulates mechanical properties of the cortex and allow rapid solid-to-fluid transitions in cell surface mechanics (Truong Quang et al, 2021). Since PCP complexes are localized in neuroectoderm at the level of adherens junction (Butler and Wallingford, 2017; Shimada et al, 2001), we propose that intra-junctional mechanical heterogeneity is coordinated through NMII activity and cadherin clustering.…”

“…We propose that NMII restricts junctional Pk2 movement by maintaining apical cortex compartmentalization. Moreover, NMII promotes mechanical heterogeneity within the junction, perhaps through the asymmetric accumulation of cadherins (Cavanaugh et al, 2022; Vanderleest et al, 2018) or by spatial control of fluid-solid transitions in the cortical actomyosin cytoskeleton (Truong Quang et al, 2021). This role of NMII, distinct from its involvement in contractility and modulation of junctional tension, leads to asymmetric repulsion of Pk2 puncta from posterior vertices.…”

Actomyosin-Driven Division of a Synthetic Cell

“…There is evidence that the actin cortex itself is stratified, with myosin filaments being restricted toward the cytoplasmic side of the cortex due to steric exclusion from the dense cortex. 149 Interestingly, a recent in vitro reconstitution study showed that actin−myosin networks on SLBs spontaneously self-organize into radial actin structures (asters) with myosin at the core and layered atop to relieve steric constraints. 150 Mechanical measurements on cells indicate that the cortex adheres to the membrane via a high density of weak links.…”

Macrophage migrates on alternate non-adhesive surfaces

“…Therefore, activation of the Rho-ROCK-myosin IIA pathway played a negative role in podosome formation and macrophage motility on the alternate non-adhesive surface. Spatial coordination of myosin and actin at the cortex regulates cell surface mechanics (18). Hence, we analyzed the relative localization of cortical actin and myosin IIA in macrophages on the alternate non-adhesive surface.…”