How negative feedback from filamentous actin affects cell shapes and motility

TL;DR

This paper investigates how negative feedback from filamentous actin influences cell shapes and motility, revealing multiple cell states and transitions driven by a PDE model and simulations.

Contribution

It introduces a PDE model incorporating negative feedback from F-actin to GTPase, analyzing its impact on cell shape dynamics and motility modes.

Findings

Identification of resting, polar, and traveling wave cell states.

Coexistence of multiple cell behaviors in certain parameters.

Transitions between cell states triggered by noise.

Abstract

The crawling motility of many eukaryotic cells is driven by filamentous actin (F-actin), and regulated by a network of signaling proteins and lipids (including small GTPases). The tangle of positive and negative feedback loops gives rise to various experimentally observed dynamic patterns (``actin waves''). Here we consider a recent prototypical model for actin waves in which F-actin exerts negative feedback onto a GTPase. Guided by recent numerical PDE bifurcation analysis in Hughes (2025) and Hughes et al (2026), we explore cell shapes and motility associated with polar, oscillatory, and traveling waves solutions of a mass-conserved partial differential equation (PDE) model. We use Morpheus (cellular Potts) simulations to investigate the implications of such regimes of behavior on the shapes and motion of cells, and on transitions between modes of behavior. The model demonstrates various cell states, including resting (spatially uniform GTPase), polar cells (static ``zones'' of GTPase), and traveling waves along the cell edge. In some parameter regimes, such states can coexist, so that cells can transition from one behavior to another in response to noisy stimuli.