Myosin II Controls Cellular Branching Morphogenesis and Migration in 3D by Minimizing Plasma Membrane Curvature

Abstract

We adopted high-resolution imaging, computer vision, and mathematical morphology to quantify branching morphogenesis in primary aortic endothelial cells migrating in 3D collagen matrices. We find that myosin-II activity regulates both global branch complexity and local cell surface curvature. Myosin-II preferentially assembles onto cortical regions of minimal membrane curvature while also acting to minimize local curvature. Analysis of temporal relationships between morphometric parameters demonstrate that cycles of exploratory branching, followed by branch pruning and cell body advance are driven by cycles of myosin II dissociation from the cortex that allow plasma membrane protrusion, followed by myosin II cortical recruitment to drive curvature minimization. Differential association of myosin to the inner high-curvature and outer low-curvature surfaces of branch bases control branch orientation, linking local curvature control to directional control of migration. Thus, membrane curvature minimization by myosin II is a critical mechanism of dynamic cell shape control for guiding migration in 3D.