Collective durotaxis of cohesive cell clusters on a stiffness gradient

TL;DR

This paper presents a theoretical model explaining how cohesive cell monolayers collectively migrate toward stiffer substrates, revealing various dynamical behaviors and providing insights for future experimental design.

Contribution

The study introduces a continuum active polar fluid model that predicts collective durotaxis and explores its dynamical regimes, advancing understanding of tissue migration on stiffness gradients.

Findings

Model predicts collective durotaxis in cell monolayers.

Identifies regimes of spreading and contraction during migration.

Provides exact solutions offering physical insights and experimental guidance.

Abstract

Many types of motile cells perform durotaxis, namely, directed migration following gradients of substrate stiffness. Recent experiments have revealed that cell monolayers can migrate toward stiffer regions even when individual cells do not -- a phenomenon known as collective durotaxis. Here we address the spontaneous motion of finite cohesive cell monolayers on a stiffness gradient. We theoretically analyze a continuum active polar fluid model that has been tested in recent wetting assays of epithelial tissues, and includes two types of active forces (cell-substrate traction and cell-cell contractility). The competition between the two active forces determines whether a cell monolayer spreads or contracts. Here, we show that this model generically predicts collective durotaxis, and that it features a variety of dynamical regimes as a result of the interplay between the spreading state and the global propagation, including sequential contraction and spreading of the monolayer as it moves toward higher stiffness. We solve the model exactly in some relevant cases, which provides both physical insights into the mechanisms of tissue durotaxis and spreading as well as a variety of predictions that could guide the design of future experiments.