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Nat Cell Biol. 2015 Apr;17(4):409-20. doi: 10.1038/ncb3135.

Control of cell-cell forces and collective cell dynamics by the intercellular adhesome.

Author information

1
Institute for Bioengineering of Catalonia, Barcelona 08028, Spain.
2
1] Institute for Bioengineering of Catalonia, Barcelona 08028, Spain [2] Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, and CIBERES, Barcelona 08036, Spain.
3
Laboratori de Càlcul Numèric, Department of Applied Mathematics III, Universitat Politècnica de Catalunya, Barcelona 08036, Spain.
4
Departament d'Enginyeria Química, Universitat Rovira i Virgili, Tarragona 43007, Catalonia, Spain.
5
1] Departament d'Enginyeria Química, Universitat Rovira i Virgili, Tarragona 43007, Catalonia, Spain [2] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain.
6
1] Institute for Bioengineering of Catalonia, Barcelona 08028, Spain [2] Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, and CIBERES, Barcelona 08036, Spain [3] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain.

Abstract

Dynamics of epithelial tissues determine key processes in development, tissue healing and cancer invasion. These processes are critically influenced by cell-cell adhesion forces. However, the identity of the proteins that resist and transmit forces at cell-cell junctions remains unclear, and how these proteins control tissue dynamics is largely unknown. Here we provide a systematic study of the interplay between cell-cell adhesion proteins, intercellular forces and epithelial tissue dynamics. We show that collective cellular responses to selective perturbations of the intercellular adhesome conform to three mechanical phenotypes. These phenotypes are controlled by different molecular modules and characterized by distinct relationships between cellular kinematics and intercellular forces. We show that these forces and their rates can be predicted by the concentrations of cadherins and catenins. Unexpectedly, we identified different mechanical roles for P-cadherin and E-cadherin; whereas P-cadherin predicts levels of intercellular force, E-cadherin predicts the rate at which intercellular force builds up.

PMID:
25812522
PMCID:
PMC4886824
DOI:
10.1038/ncb3135
[Indexed for MEDLINE]
Free PMC Article

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