A theory for coexistence and selection of branched actin networks in a shared and finite pool of monomers

TL;DR

This paper presents a theoretical model explaining how branched actin networks coexist and compete for shared monomers, highlighting local depletion as a key universal factor in their regulation.

Contribution

It introduces a minimal ODE-based theory demonstrating how local monomer depletion leads to coexistence or selection among actin networks without complex molecular assumptions.

Findings

Local depletion causes negative feedback in network growth.

The model predicts stable coexistence and conditions for selection.

Simulations confirm the theory's predictions even with large monomer pools.

Abstract

Cellular actin structures are continuously turned over while keeping similar sizes. Since they all compete for a shared pool of actin monomers, the question arises how they can coexist in these dynamic steady states. Recently, the coexistence of branched actin networks with different densities growing in a shared and finite pool of purified proteins has been demonstrated in a biomimetic bead assay. However, theoretical work in the context of organelle size regulation has mainly been focused on linear architectures, such as single filaments and bundles, and thus is not able to explain this observation. Here we show theoretically that the local depletion of actin monomers caused by the growth of a branched network naturally gives rise to a negative feedback loop between network density and growth rate, and that this competition is captured by one central ordinary differential equation. A comprehensive bifurcation analysis shows that the theory leads to well-defined steady states even in the case of multiple networks sharing the same pool of monomers, without any need for specific molecular processes. Under increasing competition strength, coexistence is replaced by selection. We also show that our theory is in excellent agreement with spatiotemporal simulations, implemented in a finite element framework, and that local depletion even occurs in the presence of a large pool of non-polymerizable actin. In summary, our work suggests that local monomer depletion is the decisive and universal factor controlling growth of branched actin networks.