title: Endocytic reawakening of motility in jammed epithelia.
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.
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Via Adamello, 16 20139, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Malinverno
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Via Adamello, 16 20139, Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Corallino
authors.affiliation: Università degli Studi di Milano, Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, I-20090, Segrate, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Giavazzi
authors.affiliation: ETH Zurich, Laboratory of Thermodynamics in Emerging Technologies Sonneggstrasse 3,8092 Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Bergert
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Via Adamello, 16 20139, Milan, Italy.
authors.forename: Qingsen
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institut Curie, 26 rue d'Ulm 75248 PARIS CEDEX 05 - France.
authors.forename: Marco
authors.initials: M
authors.lastname: Leoni
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Via Adamello, 16 20139, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Disanza
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Via Adamello, 16 20139, Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Frittoli
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Via Adamello, 16 20139, Milan, Italy.
authors.forename: Amanda
authors.initials: A
authors.lastname: Oldani
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Via Adamello, 16 20139, Milan, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Martini
authors.affiliation: ETH Zurich, Laboratory of Thermodynamics in Emerging Technologies Sonneggstrasse 3,8092 Zurich, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Lendenmann
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Via Adamello, 16 20139, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Deflorian
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Via Adamello, 16 20139, Milan, Italy.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Beznoussenko
authors.affiliation: ETH Zurich, Laboratory of Thermodynamics in Emerging Technologies Sonneggstrasse 3,8092 Zurich, Switzerland.
authors.forename: Dimos
authors.initials: D
authors.lastname: Poulikakos
authors.affiliation: Institute of Molecular and Cell Biology (IMCB), A(∗)STAR, Singapore 138673, Singapore.
authors.forename: Ong Kok
authors.initials: OK
authors.lastname: Haur
authors.affiliation: 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.
authors.forename: Marina
authors.initials: M
authors.lastname: Uroz
authors.affiliation: 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.
authors.forename: Xavier
authors.initials: X
authors.lastname: Trepat
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Via Adamello, 16 20139, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Parazzoli
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Via Adamello, 16 20139, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Maiuri
authors.affiliation: Institute of Molecular and Cell Biology (IMCB), A(∗)STAR, Singapore 138673, Singapore.
authors.forename: Weimiao
authors.initials: W
authors.lastname: Yu
authors.affiliation: ETH Zurich, Laboratory of Thermodynamics in Emerging Technologies Sonneggstrasse 3,8092 Zurich, Switzerland.
authors.forename: Aldo
authors.initials: A
authors.lastname: Ferrari
authors.affiliation: Università degli Studi di Milano, Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, I-20090, Segrate, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cerbino
authors.affiliation: IFOM-FIRC Institute of Molecular Oncology, Via Adamello, 16 20139, Milan, Italy.|Università degli Studi di Milano, Dipartimento di Oncologia e Emato-Oncologia , I-20133, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scita
mesh_terms: D001696:Biomechanical Phenomena; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D004848:Epithelium / Q000378:metabolism*; D006801:Humans; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D020696:rab5 GTP-Binding Proteins