Role of contact inhibition of locomotion and junctional mechanics in epithelial collective responses to injury

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Title: Role of contact inhibition of locomotion and junctional mechanics in epithelial collective responses to injury
Authors: Coburn, Luke
Lopez, Hender
Schouwenaar, Irin-Maya
et al.
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Date: 25-Jan-2018
Online since: 2019-05-09T11:13:51Z
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 to injuries by reorganizing their cell-cell junctions and migrating directionally towards the sites of damage. Notwithstanding, the mechanisms that drive collective responses in epithelial aggregates remain poorly understood. In this work, we develop a minimal mechanistic model that is able to capture the essential features of epithelial collective responses to injuries. We show that a model that integrates the mechanics of cells at the cell-cell and cell-substrate interfaces as well as contact inhibition of locomotion (CIL) correctly predicts two key properties of epithelial response to injury as: (1) local relaxation of the tissue and (2) collective reorganization involving the extension of cryptic lamellipodia that extend, on average, up to 3 cell diameters from the site of injury and morphometric changes in the basal regions. Our model also suggests that active responses (like the actomyosin purse string and softening of cell-cell junctions) are needed to drive morphometric changes in the apical region. Therefore, our results highlight the importance of the crosstalk between junctional biomechanics, cell substrate adhesion, and CIL, as well as active responses, in guiding the collective rearrangements that are required to preserve the epithelial barrier in response to injury.
Funding Details: European Commission - European Regional Development Fund
Higher Education Authority
Irish Research Council
Type of material: Journal Article
Publisher: IOP Publishing
Journal: Physical Biology
Volume: 15
Issue: 2
Start page: 024001
Copyright (published version): 2018 the Authors
Keywords: Contact inhibition of locomotionJunctional tensionCell adhesionCollective responsesWound repairEpithelial cellsIntercellular junctionsBiomechanical phenomena
DOI: 10.1088/1478-3975/aa976b
Language: en
Status of Item: Peer reviewed
Appears in Collections:Physics Research Collection

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