# The mechanism of dynamic steady states in lamellipodia

## TL;DR

This paper uses simulations to explain how lamellipodia maintain a stable, dynamic structure through a balance of actin assembly and disassembly.

## Contribution

The study reveals that F-actin severing and parameter adjustments are key to maintaining dynamic steady states in lamellipodia.

## Key findings

- F-actin severing is crucial for maintaining a continuous retrograde flow by enhancing disassembly.
- Different modes of dynamic steady states are possible in the branched actin network.
- Perturbations disrupting steady states can be compensated by altering other key parameters.

## Abstract

Lamellipodia are quasi-two-dimensional actin projections formed on the leading edge of the cell, playing an important role in sensing surrounding mechanical environments by forming focal adhesions. A branched actin network in the lamellipodia exhibits a stable, yet 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. Using an agent-based computational model, we probed how physical interactions between subcellular components in the lamellipodia mediate and sustain the dynamic steady state. We simulated the branched network found in the lamellipodia, consisting of F-actin, myosin motor, Arp2/3 complex, and actin cross-linking protein, on an elastic substrate. We reproduced a steady retrograde flow induced by myosin activity and balanced by the interplay between network assembly and disassembly, but hindered by resistances from adhesions formed on the underlying substrate. We found that F-actin severing is crucial for maintaining a continuous, uniform retrograde flow because it enhances the disassembly of actin bundle/arc formed due to network contraction at the rear. In addition, 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.

This study investigates the adaptive mechanisms that maintain the dynamic steady state conditions in the lamellipodia. Using simulations of the branched actin network, we found that the balance between actin assembly and disassembly, and the competition between contractile forces and frictional forces govern the steady state conditions with continuous actin retrograde flow. We further found that the branched actin network can exhibit different modes of dynamic steady states, where perturbations preventing steady state can be compensated by adjusting other key parameters. This work advances our understanding of the complex interplay between subcellular components in lamellipodia, providing new insights into the adaptive robustness of the branched actin network in response to environmental changes.