Endocytic reawakening of motility in jammed epithelia.

Dynamics of epithelial monolayers has recently been interpreted in terms of a jamming or rigidity transition. How cells control such phase transitions is, however, unknown. Here we show that RAB5A, a key endocytic protein, is sufficient to induce large-scale, coordinated motility over tens of cells,...

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Detalhes bibliográficos
Autores: Malinverno, Chiara, Corallino, Salvatore, Giavazzi, Fabio, Bergert, Martin, Li, Qingsen, Leoni, Marco, Disanza, Andrea, Frittoli, Emanuela, Oldani, Amanda, Martini, Emanuele, Lendenmann, Tobias, Deflorian, Gianluca, Beznoussenko, Galina V., Poulikakos, Dimos, ONG Kok Haur, Uroz, Marina, Trepat Guixer, Xavier, Parazzoli, Dario, Maiuri, Paolo, Yu, Weimiao, Ferrari, Aldo, Cerbino, Roberto, Scita, Giorgio
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2017
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/120682
Acesso em linha:https://hdl.handle.net/2445/120682
Access Level:acceso abierto
Palavra-chave:Epiteli
Proteïnes
Motilitat cel·lular
Epithelium
Proteins
Cell motility
Descrição
Resumo:Dynamics of epithelial monolayers has recently been interpreted in terms of a jamming or rigidity transition. How cells control such phase transitions is, however, unknown. Here we show that RAB5A, a key endocytic protein, is sufficient to induce large-scale, coordinated motility over tens of cells, and ballistic motion in otherwise kinetically arrested monolayers. This is linked to increased traction forces and to the extension of cell protrusions, which align with local velocity. Molecularly, impairing endocytosis, macropinocytosis or increasing fluid efflux abrogates RAB5A-induced collective motility. A simple model based on mechanical junctional tension and an active cell reorientation mechanism for the velocity of self-propelled cells identifies regimes of monolayer dynamics that explain endocytic reawakening of locomotion in terms of a combination of large-scale directed migration and local unjamming. These changes in multicellular dynamics enable collectives to migrate under physical constraints and may be exploited by tumours for interstitial dissemination.