The Mechanism of Dynamic Steady States in Lamellipodia

Abstract

Lamellipodia are quasi-two-dimensional actin projections formed on the leading edge of the cell, playing an important role 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, which is attributed to a balance between network assembly at the leading edge and disassembly at the rear. Although the molecular players and architecture of the lamellipodia have been investigated extensively during recent decades, it still remains elusive how the dynamic steady state with continuous retrograde flow is achieved and robustly maintained. In this study, using an agent-based computational model, we probed how physical interactions between subcellular components in the lamellipodia lead to the dynamic steady state. We reproduced a steady retrograde flow induced by myosin activity and balance between network assembly and disassembly but hindered by resistances from adhesions formed on the underlying substrate. We demonstrated that different modes of dynamic steady states are possible, and that a network which failed to show the retrograde flow due to perturbations can be rescued by altering other factors. Our study provides insights into understanding how cells maintain the dynamic steady state of the lamellipodia in highly varying microenvironments.