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Force measurements in E-cadherin–mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through Rac and Cdc42

We have used a modified, dual pipette assay to quantify the strength of cadherin-dependent cell–cell adhesion. The force required to separate E-cadherin–expressing paired cells in suspension was measured as an index of intercellular adhesion. Separation force depended on the homophilic interaction o...

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Autores principales: Chu, Yeh-Shiu, Thomas, William A., Eder, Olivier, Pincet, Frederic, Perez, Eric, Thiery, Jean Paul, Dufour, Sylvie
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172605/
https://www.ncbi.nlm.nih.gov/pubmed/15596540
http://dx.doi.org/10.1083/jcb.200403043
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author Chu, Yeh-Shiu
Thomas, William A.
Eder, Olivier
Pincet, Frederic
Perez, Eric
Thiery, Jean Paul
Dufour, Sylvie
author_facet Chu, Yeh-Shiu
Thomas, William A.
Eder, Olivier
Pincet, Frederic
Perez, Eric
Thiery, Jean Paul
Dufour, Sylvie
author_sort Chu, Yeh-Shiu
collection PubMed
description We have used a modified, dual pipette assay to quantify the strength of cadherin-dependent cell–cell adhesion. The force required to separate E-cadherin–expressing paired cells in suspension was measured as an index of intercellular adhesion. Separation force depended on the homophilic interaction of functional cadherins at the cell surface, increasing with the duration of contact and with cadherin levels. Severing the link between cadherin and the actin cytoskeleton or disrupting actin polymerization did not affect initiation of cadherin-mediated adhesion, but prevented it from developing and becoming stronger over time. Rac and Cdc42, the Rho-like small GTPases, were activated when E-cadherin–expressing cells formed aggregates in suspension. Overproduction of the dominant negative form of Rac or Cdc42 permitted initial E-cadherin–based adhesion but affected its later development; the dominant active forms prevented cell adhesion outright. Our findings highlight the crucial roles played by Rac, Cdc42, and actin cytoskeleton dynamics in the development and regulation of strong cell adhesion, defined in terms of mechanical forces.
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spelling pubmed-21726052008-03-05 Force measurements in E-cadherin–mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through Rac and Cdc42 Chu, Yeh-Shiu Thomas, William A. Eder, Olivier Pincet, Frederic Perez, Eric Thiery, Jean Paul Dufour, Sylvie J Cell Biol Research Articles We have used a modified, dual pipette assay to quantify the strength of cadherin-dependent cell–cell adhesion. The force required to separate E-cadherin–expressing paired cells in suspension was measured as an index of intercellular adhesion. Separation force depended on the homophilic interaction of functional cadherins at the cell surface, increasing with the duration of contact and with cadherin levels. Severing the link between cadherin and the actin cytoskeleton or disrupting actin polymerization did not affect initiation of cadherin-mediated adhesion, but prevented it from developing and becoming stronger over time. Rac and Cdc42, the Rho-like small GTPases, were activated when E-cadherin–expressing cells formed aggregates in suspension. Overproduction of the dominant negative form of Rac or Cdc42 permitted initial E-cadherin–based adhesion but affected its later development; the dominant active forms prevented cell adhesion outright. Our findings highlight the crucial roles played by Rac, Cdc42, and actin cytoskeleton dynamics in the development and regulation of strong cell adhesion, defined in terms of mechanical forces. The Rockefeller University Press 2004-12-20 /pmc/articles/PMC2172605/ /pubmed/15596540 http://dx.doi.org/10.1083/jcb.200403043 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Chu, Yeh-Shiu
Thomas, William A.
Eder, Olivier
Pincet, Frederic
Perez, Eric
Thiery, Jean Paul
Dufour, Sylvie
Force measurements in E-cadherin–mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through Rac and Cdc42
title Force measurements in E-cadherin–mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through Rac and Cdc42
title_full Force measurements in E-cadherin–mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through Rac and Cdc42
title_fullStr Force measurements in E-cadherin–mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through Rac and Cdc42
title_full_unstemmed Force measurements in E-cadherin–mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through Rac and Cdc42
title_short Force measurements in E-cadherin–mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through Rac and Cdc42
title_sort force measurements in e-cadherin–mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through rac and cdc42
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172605/
https://www.ncbi.nlm.nih.gov/pubmed/15596540
http://dx.doi.org/10.1083/jcb.200403043
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