Lamellipodia are two-dimensional actin protrusions observed at the leading edge of the cell, playing an important role in cell migration and in sensing surrounding environments by forming focal adhesions. A branched actin network in the lamellipodia exhibits a stable dynamic steady state characterized by a retrograde flow. This dynamic state is attributed to balance between network assembly at the leading edge and network disassembly at the rear. Although the molecular players and architecture of the lamellipodia have been understood relatively well, it still remains unclear how the dynamic steady state is robustly maintained. Using an agent-based computational model, we investigated how molecular interactions between subcellular components in the lamellipodia induce and maintain the dynamic steady state. We simulated the branched network consisting of actin filaments, myosin motors, Arp2/3 complexes, and actin cross-linking proteins, on a substrate. We reproduced a steady retrograde flow resulting from actin polymerization, myosin activity, and balance between network assembly and disassembly. The flow was obstructed by resistances from adhesions formed on the underlying substrate. We found that disassembly induced by filament severing is crucial for maintaining a continuous retrograde flow since the severing increases the disassembly rate of actin bundle/arc emerging due to network contraction at the rear. In addition, we showed that different modes of dynamic steady states can appear, and that a network which failed to show the retrograde flow due to perturbations can be rescued by changing other factors. Our study provides insights into understanding how cells maintain the dynamic steady state of the lamellipodia in highly varying microenvironments.
Kim et al. (Sun,) studied this question.