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Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):12926-12931. doi: 10.1073/pnas.1811348115. Epub 2018 Nov 30.

Spontaneous migration of cellular aggregates from giant keratocytes to running spheroids.

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Laboratoire Physico Chimie Curie, Institut Curie, PSL Research University, CNRS UMR168, 75005, Paris, France.
Sorbonne Universités, UPMC Univ Paris 06, 75005 Paris, France.
Department of Theoretical Physics, University of Geneva, CH-1211 Geneva, Switzerland.
Laboratoire de Chimie et Physique-Approche Multi-échelles des Milieux Complexes, Institut Jean Barriol, Universite de Lorraine, 57078 Metz, France.
Institut Curie, CNRS, UMR 144, 75248 Paris Cedex 05, France.
Institut de Mécanique des Fluides de Toulouse (IMFT), Université de Toulouse, CNRS, 31400 Toulouse, France.
Faculté de Médecine, Université Paris Est, 94000 Créteil, France.
Institut National de la Santé et de la Recherche Médicale, U955, 94000 Créteil, France.
Department of Physics, Yale University, New Haven, CT 06511.
Department of Biomedical Engineering, Yale University, New Haven, CT 06511.
Systems Biology Institute, Yale University, West Haven, CT 06516.
Laboratoire Physico Chimie Curie, Institut Curie, PSL Research University, CNRS UMR168, 75005, Paris, France;


Despite extensive knowledge on the mechanisms that drive single-cell migration, those governing the migration of cell clusters, as occurring during embryonic development and cancer metastasis, remain poorly understood. Here, we investigate the collective migration of cell on adhesive gels with variable rigidity, using 3D cellular aggregates as a model system. After initial adhesion to the substrate, aggregates spread by expanding outward a cell monolayer, whose dynamics is optimal in a narrow range of rigidities. Fast expansion gives rise to the accumulation of mechanical tension that leads to the rupture of cell-cell contacts and the nucleation of holes within the monolayer, which becomes unstable and undergoes dewetting like a liquid film. This leads to a symmetry breaking and causes the entire aggregate to move as a single entity. Varying the substrate rigidity modulates the extent of dewetting and induces different modes of aggregate motion: "giant keratocytes," where the lamellipodium is a cell monolayer that expands at the front and retracts at the back; "penguins," characterized by bipedal locomotion; and "running spheroids," for nonspreading aggregates. We characterize these diverse modes of collective migration by quantifying the flows and forces that drive them, and we unveil the fundamental physical principles that govern these behaviors, which underscore the biological predisposition of living material to migrate, independent of length scale.


bipedal stick–slip motion; cell aggregate; collective migration; dewetting; reactive wetting

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