Contact inhibition of locomotion and junctional mechanics guide collective cell behavior in epithelial wound repair

TL;DR

This study investigates how junctional mechanics, cell-substrate adhesion, and contact inhibition of locomotion coordinate to drive collective epithelial cell responses during wound repair, combining experimental analysis with computational modeling.

Contribution

It introduces a computational model that integrates junctional and substrate mechanics to predict epithelial tissue responses to injury, emphasizing the role of contact inhibition of locomotion.

Findings

Model predicts local tissue relaxation after injury

Elongation of cells and cryptic lamellipodia extend from injury site

Junctional biomechanics and contact inhibition guide collective repair

Abstract

Epithelial tissues form physically integrated barriers against the external environment protecting organs from infection and invasion. Within each tissue, epithelial cells respond to different challenges that can potentially compromise tissue integrity. In particular, cells collectively respond by reorganizing their cell-cell junctions and migrating directionally towards the sites of injury. Notwithstanding, the mechanisms that define the spatiotemporal scales and driving forces of these collective responses remain poorly understood. To address this we first analyzed the collective response of epithelial monolayers to injury and compare the results with different computational models of epithelial cells. We found that a model that integrates the mechanics of cells at the cell-cell and cell-substrate interface as well as contact inhibition of locomotion predicts two key properties of epithelial response to injury as: 1) local relaxation of the tissue and 2) collective responses involving the elongation of cells (basal and apical regions) and extension of cryptic lamellipodia that extend up to < 3 cell diameters from the site of injury. Our results therefore highlight the integration between junctional biomechanics, cell substrate adhesion and contact inhibition of locomotion to guide the rapid collective rearrangements that are required to preserve the epithelial barrier in response to injury.