Stick-Slip model for actin-driven cell protrusions, cell polarisation and crawling

TL;DR

This paper presents a stick-slip model based on the molecular clutch concept that explains the dynamic behaviors of cell protrusions, polarization, and crawling by coupling adhesion mechanics with cellular forces, reproducing observed patterns.

Contribution

It introduces a novel analytical model linking adhesion dynamics and cellular mechanics to explain complex cell motility behaviors.

Findings

Traction forces exhibit stick-slip dynamics causing protrusion/retraction waves.

Spontaneous symmetry breaking and polarization can occur without external cues.

Membrane tension facilitates long-range mechanical communication for symmetry breaking.

Abstract

Cell crawling requires the generation of intracellular forces by the cytoskeleton and their transmission to an extracellular substrate through specific adhesion molecules. Crawling cells show many features of excitable systems, such as spontaneous symmetry breaking and crawling in the absence of external cues, and periodic and propagating waves of activity. Mechanical instabilities in the active cytoskeleton network and feedback loops in the biochemical network of activators and repressors of cytoskeleton dynamics have been invoked to explain these dynamical features. Here, we show that the interplay between the dynamics of cell-substrate adhesion and linear cellular mechanics is sufficient to reproduce many non-linear dynamical patterns observed in spreading and crawling cells. Using an analytical formalism of the molecular clutch model of cell adhesion, regulated by local mechanical forces, we show that cellular traction forces exhibit a stick-slip dynamics resulting in periodic waves of protrusion/retraction and propagating waves along the cell edge. This can explain spontaneous symmetry breaking and polarisation of spreading cells, leading to steady crawling or bipedal motion, and bistability, where persistent cell motion requires a sufficiently strong transient external stimulus. The model also highlight the role of membrane tension in providing the long-range mechanical communication across the cell required for symmetry breaking.