Gap geometry dictates epithelial closure efficiency
We thank group members from MBI Rene-Marc Mege and W.J. Nelson for helpful discussions. We also thank MBI Microfabrication (Gianluca Grenci and Mohammed Asraf), MBI Science Communication Core (Larisa Bulavina, Andrew Wong and Steven Wolf) and MBI Microscopy Core (Felix Margadant) for continuous support. We are grateful to S. Yonemura and W.J. Nelson for their generous gift of MDCK cell lines and to Michael W. Davidson and Pakorn Kanchanawong for mApple-paxillin plasmid. Financial supports from the Human Frontier Science Program (grant RGP0040/2012), the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 617233, Agence Nationale pour la Recherche project REGENR (grant ANR-11-BSV5-0021), Pessoa programme (project 30920XM) and the Mechanobiology Institute are gratefully acknowledged. XT acknowledges Spanish Ministry of Economy and Competitiveness (BFU2012-38146), the Generalitat de Catalunya (2014-SGR-927), and the European Research Council (CoG-616480). B.L. acknowledges the Institut Universitaire de France and T.C. the USPC-NUS agreement for his fellowship. ; 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. ; publishersversion ; published