Modeling of protrusion phenotypes driven by the actin-membrane interaction.

We propose a mathematical model for simulating the leading-edge dynamics of a migrating cell from the interplay among elastic properties, architecture of the actin cytoskeleton, and the mechanics of the membrane. Our approach is based on the description of the length and attachment dynamics of actin filaments in the lamellipodium network. It is used to determine the total force exerted on the membrane at each position along the leading edge and at each time step. The model reproduces the marked state switches in protrusion morphodynamics found experimentally between epithelial cells in control conditions and cells expressing constitutively active Rac, a signaling molecule involved in the regulation of lamellipodium network assembly. The model also suggests a mechanistic explanation of experimental distortions in protrusion morphodynamics induced by deregulation of Arp2/3 and cofilin activity.