Low-Dimensional Manifold of Actin Polymerization Dynamics

TL;DR

This paper introduces two low-dimensional, linear models of actin filament polymerization dynamics, providing exact solutions that clarify the system's behavior and timescale interactions, advancing understanding of actin cytoskeleton regulation.

Contribution

The authors develop two novel linear, low-dimensional models of actin filament dynamics that enable exact solutions and deeper analytical insights, improving upon previous nonlinear models.

Findings

Exact solutions for the reduced models are derived.

The models reveal the ordering of timescales in actin dynamics.

Steady-state behavior depends on initial conditions in specific ways.

Abstract

Actin filaments are critical components of the eukaryotic cytoskeleton, playing important roles in a number of cellular functions, such as cell migration, organelle transport, and mechanosensation. They are helical polymers with a well-defined polarity, composed of globular monomers that bind nucleotides in one of three hydrolysis states (ATP, ADP-Pi, or ADP). Mean-field models of the dynamics of actin polymerization have succeeded in, among other things, determining the nucleotide profile of an average filament and resolving the mechanisms of accessory proteins, however these models require numerical solution of a high-dimensional system of nonlinear ODE's. By truncating a set of recursion equations, the Brooks-Carlsson model reduces dimensionality to 11, but it remains nonlinear and does not admit an analytical solution, hence, significantly hindering understanding of its resulting dynamics. In this work, by taking advantage of the fast timescales of the hydrolysis states of the filament tips, we propose two model reduction schemes that achieve low dimensionality and linearity. We provide an exact solution of the resulting linear equations and use it to shed light on the dynamical behaviors of the full BC model, highlighting the relative ordering of the timescales of various collective processes, and explaining some unusual dependence of the steady-state behavior on initial conditions.