Mechanics of motility initiation and motility arrest in crawling cells

TL;DR

This paper presents a simplified 1D model explaining how cells initiate and arrest crawling motility through contractility and adhesion dynamics, aligning with experimental observations in keratocytes.

Contribution

It introduces a minimal analytical model linking contractility, adhesion, and symmetry breaking in cell motility, predicting re-symmetrization at high contractility levels.

Findings

Model reproduces keratocyte motility patterns

Reveals nonlocal feedback between mechanics and active agent transport

Predicts cell re-symmetrization at high contractility levels

Abstract

Motility initiation in crawling cells requires transformation of a symmetric state into a polarized state. In contrast, motility arrest is associated with re-symmetrization of the internal configuration of a cell. Experiments on keratocytes suggest that polarization is triggered by the increased contractility of motor proteins but the conditions of re-symmetrization remain unknown. In this paper we show that if adhesion with the extra-cellular substrate is sufficiently low, the progressive intensification of motor-induced contraction may be responsible for both transitions: from static (symmetric) to motile (polarized) at a lower contractility threshold and from motile (polarized) back to static (symmetric) at a higher contractility threshold. Our model of lamellipodial cell motility is based on a 1D projection of the complex intra-cellular dynamics on the direction of locomotion. In the interest of analytical transparency we also neglect active protrusion and view adhesion as passive. Despite the unavoidable oversimplifications associated with these assumptions, the model reproduces quantitatively the motility initiation pattern in fish keratocytes and reveals a crucial role played in cell motility by the nonlocal feedback between the mechanics and the transport of active agents. A prediction of the model that a crawling cell can stop and re-symmetrize when contractility increases sufficiently far beyond the motility initiation threshold still awaits experimental verification.