Gap geometry dictates epithelial closure efficiency

Andrea Ravasio, Ibrahim Cheddadi, Tianchi Chen, Telmo Pereira, Hui Ting Ong, Cristina Bertocchi, Agusti Brugues, Antonio Jacinto, Alexandre J. Kabla, Yusuke Toyama, Xavier Trepat, Nir Gov, Luís Neves de Almeida () and Benoit Ladoux ()
Additional contact information
Andrea Ravasio: Mechanobiology Institute, National University of Singapore
Ibrahim Cheddadi: Sorbonne Universités, UPMC University Paris 06, CNRS UMR 7598, Laboratoire Jacques-Louis Lions
Tianchi Chen: Mechanobiology Institute, National University of Singapore
Telmo Pereira: CEDOC - Chronic Diseases Research Center, NOVA Medical School, Rua Camara Pestana, 6, Lisbon
Hui Ting Ong: Mechanobiology Institute, National University of Singapore
Cristina Bertocchi: Mechanobiology Institute, National University of Singapore
Agusti Brugues: ICREA at Institute for Bioengineering of Catalonia and Universitat de Barcelona
Antonio Jacinto: CEDOC - Chronic Diseases Research Center, NOVA Medical School, Rua Camara Pestana, 6, Lisbon
Alexandre J. Kabla: University of Cambridge
Yusuke Toyama: Mechanobiology Institute, National University of Singapore
Xavier Trepat: ICREA at Institute for Bioengineering of Catalonia and Universitat de Barcelona
Nir Gov: Weizmann Institute of Science
Luís Neves de Almeida: Sorbonne Universités, UPMC University Paris 06, CNRS UMR 7598, Laboratoire Jacques-Louis Lions
Benoit Ladoux: Mechanobiology Institute, National University of Singapore

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract Closure of wounds and gaps in tissues is fundamental for the correct development and physiology of multicellular organisms and, when misregulated, may lead to inflammation and tumorigenesis. To re-establish tissue integrity, epithelial cells exhibit coordinated motion into the void by active crawling on the substrate and by constricting a supracellular actomyosin cable. Coexistence of these two mechanisms strongly depends on the environment. However, the nature of their coupling remains elusive because of the complexity of the overall process. Here we demonstrate that epithelial gap geometry in both in vitro and in vivo regulates these collective mechanisms. In addition, the mechanical coupling between actomyosin cable contraction and cell crawling acts as a large-scale regulator to control the dynamics of gap closure. Finally, our computational modelling clarifies the respective roles of the two mechanisms during this process, providing a robust and universal mechanism to explain how epithelial tissues restore their integrity.

Date: 2015
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DOI: 10.1038/ncomms8683

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