Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- And non-cellautonomous outside-in signaling

Darwesh Mohideen Kaderbatcha Aladin, Yeh Shiu Chu, Shuo Shen, Robert Charles Robinson, Sylvie Dufour, Virgile Viasnoff, Nicolas Borghi, Jean Paul Thiery

Research output: Contribution to journalArticlepeer-review

Abstract

Cadherins control intercellular adhesion in most metazoans. In vertebrates, intercellular adhesion differs considerably between cadherins of type-I and type-II, predominantly due to their different extracellular regions. Yet, intercellular adhesion critically depends on actomyosin contractility, in which the role of the cadherin extracellular region is unclear. Here, we dissect the roles of the Extracellular Cadherin (EC) Ig-like domains by expressing chimeric E-cadherin with E-cadherin and cadherin-7 Ig-like domains in cells naturally devoid of cadherins. Using cell-cell separation, cortical tension measurement, tissue stretching and migration assays, we show that distinct EC repeats in the extracellular region of cadherins differentially modulate epithelial sheet integrity, cell-cell separation forces, and cell cortical tension with the Cdc42 pathway, which further differentially regulate epithelial tensile strength, ductility, and ultimately collective migration. Interestingly, dissipative processes rather than static adhesion energy mostly dominate cell-cell separation forces. We provide a framework for the emergence of epithelial phenotypes from cell mechanical properties dependent on EC outside-in signaling.

Original languageEnglish
Article numbere0260593
JournalPloS one
Volume16
Issue number12 December
DOIs
Publication statusPublished - Dec 2021
Externally publishedYes

ASJC Scopus subject areas

  • General

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