Journal
NATURE MATERIALS
Volume 16, Issue 5, Pages 587-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NMAT4848
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Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [10168, 18621]
- MIUR (the Italian Ministry of University and Scientific Research)
- Italian Ministry of Health
- Ricerca Finalizzata [RF0235844]
- Worldwide Cancer Research [AICR-14-0335]
- European Research Council [268836, StG-CoG-616480]
- Italian Ministry of Education and Research, Futuro in Ricerca Project ANISOFT [RBFR125H0M]
- Spanish Ministry of Economy and Competitiveness [BFU2012-38146]
- Generalitat de Catalunya [2014-SGR-927]
- Fondazione Umberto Veronesi
- AIRC fellowship
- ETH-grant [ETH-12 15-1]
- European Research Council (ERC) [268836] Funding Source: European Research Council (ERC)
- ICREA Funding Source: Custom
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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.
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