title: Gap geometry dictates epithelial closure efficiency.
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.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ravasio
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, CNRS UMR 7598, Laboratoire Jacques-Louis Lions, F-75252 Paris, France.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Cheddadi
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Tianchi
authors.initials: T
authors.lastname: Chen
authors.affiliation: CEDOC - Chronic Diseases Research Center, NOVA Medical School, Rua Camara Pestana, 6, Lisbon, 1150-082 Lisbon, Portugal.
authors.forename: Telmo
authors.initials: T
authors.lastname: Pereira
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Hui Ting
authors.initials: HT
authors.lastname: Ong
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bertocchi
authors.affiliation: ICREA at Institute for Bioengineering of Catalonia and Universitat de Barcelona, 08028 Barcelona, Spain.
authors.forename: Agusti
authors.initials: A
authors.lastname: Brugues
authors.affiliation: CEDOC - Chronic Diseases Research Center, NOVA Medical School, Rua Camara Pestana, 6, Lisbon, 1150-082 Lisbon, Portugal.
authors.forename: Antonio
authors.initials: A
authors.lastname: Jacinto
authors.affiliation: Department of Engineering, University of Cambridge, Cambridge CB2 1PZ, UK.
authors.forename: Alexandre J
authors.initials: AJ
authors.lastname: Kabla
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.|Department of Biological Sciences National University of Singapore, Singapore 117543, Singapore.|Temasek Life Sciences Laboratory, Singapore 117604, Singapore.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Toyama
authors.affiliation: ICREA at Institute for Bioengineering of Catalonia and Universitat de Barcelona, 08028 Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Trepat
authors.affiliation: Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Gov
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, CNRS UMR 7598, Laboratoire Jacques-Louis Lions, F-75252 Paris, France.|INRIA-Paris-Rocquencourt, MAMBA Team, 78153 Le Chesnay, Domaine de Voluceau BP105, France.
authors.forename: Luís
authors.initials: L
authors.lastname: Neves de Almeida
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.|Institut Jacques Monod (IJM), CNRS UMR 7592 and Université Paris Diderot, 75013 Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Ladoux
mesh_terms: D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D003198:Computer Simulation; D004285:Dogs; D004331:Drosophila melanogaster; D004847:Epithelial Cells / Q000502:physiology*; D004848:Epithelium; D005455:Fluorescent Antibody Technique; D066298:In Vitro Techniques; D000069416:Intravital Microscopy; D053685:Laser Therapy; D061985:Madin Darby Canine Kidney Cells; D008866:Microsurgery; D014945:Wound Healing / Q000502:physiology
chemical_list: D000205:Actomyosin