Discrete mechanical model of lamellipodial actin networks

Determining how mechanical forces and actin filament turnover coordinate within the lamellipodium is important for understanding cell migration. Continuum models have investigated the stress profile of lamellipodial actin networks including around focal adhesions. However, the forces and deformations of individual actin filaments important in lamellipodial mechanics have largely not been considered. We developed a filament-level computational model of an actin network undergoing retrograde flow simulated via 3d Brownian dynamics. Retrograde flow is maintained by both pushing forces at the leading edge (due to actin polymerization) and pulling forces at the back (due to molecular motors). Connectivity between actin filaments is maintained by bonds representing the Arp 2/3 complex and actin filament crosslinkers. Remodeling of the network occurs via the addition of actin filaments near the leading edge and via filament and severing. We investigate how several parameters affect the stress distribution, network deformation and retrograde flow speed of the actin network, including focal adhesion strength and crosslinking. The model reproduces actin arcs and filopodial bundle as well reduction in retrograde flow speed under cytochalasin D.