Reconstitution of actomyosin networks in cell-sized liposomes reveals distinct mechanical roles of cytoskeletal organization in membrane shape remodeling.

The actin cortex, a thin layer of actomyosin network beneath the plasma membrane, regulates various cell functions by generating active forces and inducing membrane deformations, including blebs. Although upstream signaling is involved in regulating cell shape, the extent to which downstream actomyosin molecules can control the shape remains elusive. Here, using a minimal reconstituted system with a combination of agent-based computational model, we show that while actin-membrane coupling strength determines the magnitude of membrane deformation, its balance with actin network connectivity governs the bleb initiation mechanism, either by detachment of the cortex from the membrane or by rupture of the cortex. This balance also regulates whether single or multiple blebs form. Furthermore, both experiments and simulations suggest that not only the dense cortical network but also the sparse volume-spanning network actively contributes to regulating bleb number. These findings provide mechanical insights into how cells tune actin network organization to control their shape.