Src Kinase Slows Collective Rotation of Confined Epithelial Cell Monolayers

TL;DR

This study uses optogenetics to show that activating Src kinase in confined epithelial cell monolayers slows their collective rotation, highlighting Src's role in regulating coordinated cell movement.

Contribution

It demonstrates that precise control of Src activity modulates collective cell dynamics, revealing its impact on cell adhesion and mechanical stress during migration.

Findings

Src activation halves the ratio of polar angle to friction.

Active stresses are less significant than traction forces.

Src activation increases cell-substrate adhesiveness.

Abstract

Collective cell migration is key during development, wound healing and metastasis and relies on coordinated cell behaviors at the group level. Src kinase is a key signalling protein for physiological functions of epithelia, as it regulates many cellular processes, including adhesion, motility, and mechanotransduction. Its over-activation is associated to cancer aggressiveness. Here, we take advantage of optogenetics to precisely control Src activation in time and show that its pathological-like activation slows collective rotation of epithelial cells confined into circular adhesive patches. We interpret velocity, force and stress data during period of non-activation and period of activation of Src thanks to an hydrodynamic description of the cell assembly as a polar active fluid. Src activation leads to a 2-fold decrease in the ratio of polar angle to friction, which could result from increased adhesiveness at the cell-substrate interface. Measuring internal stress allows us to show that active stresses are subdominant compared to traction forces. Our work reveals the importance of fine-tuning the level of Src activity for coordinated collective behaviors.