title: Epithelial bridges maintain tissue integrity during collective cell migration.
abstract: The ability of skin to act as a barrier is primarily determined by the efficiency of skin cells to maintain and restore its continuity and integrity. In fact, during wound healing keratinocytes migrate collectively to maintain their cohesion despite heterogeneities in the extracellular matrix. Here, we show that monolayers of human keratinocytes migrating along functionalized micropatterned surfaces comprising alternating strips of extracellular matrix (fibronectin) and non-adherent polymer form suspended multicellular bridges over the non-adherent areas. The bridges are held together by intercellular adhesion and are subjected to considerable tension, as indicated by the presence of prominent actin bundles. We also show that a model based on force propagation through an elastic material reproduces the main features of bridge maintenance and tension distribution. Our findings suggest that multicellular bridges maintain tissue integrity during wound healing when cell-substrate interactions are weak and may prove helpful in the design of artificial scaffolds for skin regeneration.
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411, Singapore.
authors.forename: Sri Ram Krishna
authors.initials: SR
authors.lastname: Vedula
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411, Singapore.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hirata
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411, Singapore.
authors.forename: Mui Hoon
authors.initials: MH
authors.lastname: Nai
authors.affiliation: Institut de Bioenginyeria de Catalunya (IBEC), ICREA, and Facultat de Medicina-Universitat de Barcelona, 08028 Barcelona, Spain.
authors.forename: Agustí
authors.initials: A
authors.lastname: Brugués
authors.affiliation: 1] Mechanobiology Institute, National University of Singapore, 117411, Singapore [2] Department of Biological Sciences, National University of Singapore and Temasek Life Sciences Laboratory, 117543, Singapore.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Toyama
authors.affiliation: Institut de Bioenginyeria de Catalunya (IBEC), ICREA, and Facultat de Medicina-Universitat de Barcelona, 08028 Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Trepat
authors.affiliation: 1] Mechanobiology Institute, National University of Singapore, 117411, Singapore [2] Department of Biomedical Engineering and Department of Mechanical Engineering, National University of Singapore, 117576, Singapore.
authors.forename: Chwee Teck
authors.initials: CT
authors.lastname: Lim
authors.affiliation: 1] Mechanobiology Institute, National University of Singapore, 117411, Singapore [2] Institut Jacques Monod (IJM), CNRS UMR 7592 and Université Paris Diderot, Paris 75013, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Ladoux
mesh_terms: D001672:Biocompatible Materials / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004129:Dimethylpolysiloxanes / Q000494:pharmacology; D004548:Elasticity; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013499:Surface Properties; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D004129:Dimethylpolysiloxanes; C013830:baysilon; D005340:Fibrinogen