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

Aladin, Darwesh Mohideen Kaderbatcha and Chu, Yeh Shiu and Shen, Shuo and Robinson, Robert Charles and Dufour, Sylvie and Viasnoff, Virgile and Borghi, Nicolas and Thiery, Jean Paul and Komarova, Yulia (2021) Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling. PLOS ONE, 16 (12). e0260593. ISSN 1932-6203

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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.

Item Type: Article
Subjects: Scholar Eprints > Biological Science
Depositing User: Managing Editor
Date Deposited: 07 Jan 2023 07:07
Last Modified: 12 Aug 2024 12:16
URI: http://repository.stmscientificarchives.com/id/eprint/473

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