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Nat Mater. 2017 May;16(5):587-596. doi: 10.1038/nmat4848. Epub 2017 Jan 30.

Endocytic reawakening of motility in jammed epithelia.

Author information

1
IFOM-FIRC Institute of Molecular Oncology, Via Adamello, 16 20139, Milan, Italy.
2
Università degli Studi di Milano, Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, I-20090, Segrate, Italy.
3
ETH Zurich, Laboratory of Thermodynamics in Emerging Technologies Sonneggstrasse 3,8092 Zurich, Switzerland.
4
Institut Curie, 26 rue d'Ulm 75248 PARIS CEDEX 05 - France.
5
Institute of Molecular and Cell Biology (IMCB), A(∗)STAR, Singapore 138673, Singapore.
6
Institute for Bioengineering of Catalonia, Barcelona, Barcelona, 08028 Spain; Catalan Institution for Research and Advanced Studies (ICREA), 08010, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain; Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain.
7
Università degli Studi di Milano, Dipartimento di Oncologia e Emato-Oncologia , I-20133, Milan, Italy.
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Contributed equally

Abstract

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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