TY - JOUR
T1 - Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- And non-cellautonomous outside-in signaling
AU - Aladin, Darwesh Mohideen Kaderbatcha
AU - Chu, Yeh Shiu
AU - Shen, Shuo
AU - Robinson, Robert Charles
AU - Dufour, Sylvie
AU - Viasnoff, Virgile
AU - Borghi, Nicolas
AU - Thiery, Jean Paul
N1 - Publisher Copyright:
© 2021 Aladin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85122042877&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0260593
DO - 10.1371/journal.pone.0260593
M3 - Article
C2 - 34937057
AN - SCOPUS:85122042877
SN - 1932-6203
VL - 16
JO - PLoS ONE
JF - PLoS ONE
IS - 12 December
M1 - e0260593
ER -