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Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694416/ https://www.ncbi.nlm.nih.gov/pubmed/34937057 http://dx.doi.org/10.1371/journal.pone.0260593 |
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author | Aladin, Darwesh Mohideen Kaderbatcha Chu, Yeh Shiu Shen, Shuo Robinson, Robert Charles Dufour, Sylvie Viasnoff, Virgile Borghi, Nicolas Thiery, Jean Paul |
author_facet | Aladin, Darwesh Mohideen Kaderbatcha Chu, Yeh Shiu Shen, Shuo Robinson, Robert Charles Dufour, Sylvie Viasnoff, Virgile Borghi, Nicolas Thiery, Jean Paul |
author_sort | Aladin, Darwesh Mohideen Kaderbatcha |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8694416 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-86944162021-12-23 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 Chu, Yeh Shiu Shen, Shuo Robinson, Robert Charles Dufour, Sylvie Viasnoff, Virgile Borghi, Nicolas Thiery, Jean Paul PLoS One Research Article 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. Public Library of Science 2021-12-22 /pmc/articles/PMC8694416/ /pubmed/34937057 http://dx.doi.org/10.1371/journal.pone.0260593 Text en © 2021 Aladin et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Aladin, Darwesh Mohideen Kaderbatcha Chu, Yeh Shiu Shen, Shuo Robinson, Robert Charles Dufour, Sylvie Viasnoff, Virgile Borghi, Nicolas Thiery, Jean Paul Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling |
title | Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling |
title_full | Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling |
title_fullStr | Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling |
title_full_unstemmed | Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling |
title_short | Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling |
title_sort | extracellular domains of e-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694416/ https://www.ncbi.nlm.nih.gov/pubmed/34937057 http://dx.doi.org/10.1371/journal.pone.0260593 |
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