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Role of contact inhibition of locomotion and junctional mechanics in epithelial collective responses to injury
Date Issued
25 January 2018
Date Available
09T11:13:51Z May 2019
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.
Sponsorship
European Commission - European Regional Development Fund
Higher Education Authority
Irish Research Council
Other Sponsorship
National Health and Medical Research Council of Australia
Australian Research Council
Australian Cancer Research Foundation
Type of Material
Journal Article
Publisher
IOP Publishing
Journal
Physical Biology
Volume
15
Issue
2
Start Page
024001
Copyright (Published Version)
2018 the Authors
Language
English
Status of Item
Peer reviewed
ISSN
1478-3967
This item is made available under a Creative Commons License
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