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.

Endocytic reawakening of motility in jammed epithelia / C. Malinverno, S. Corallino, F. Giavazzi, M. Bergert, Q. Li, M. Leoni, A. Disanza, E. Frittoli, A. Oldani, E. Martini, T. Lendenmann, G. Deflorian, G.V. Beznoussenko, D. Poulikakos, K.H. Ong, M. Uroz, X. Trepat, D. Parazzoli, P. Maiuri, W. Yu, A. Ferrari, R. Cerbino, G. Scita. - In: NATURE MATERIALS. - ISSN 1476-1122. - (2017). [Epub ahead of print]

Endocytic reawakening of motility in jammed epithelia

C. Malinverno;F. Giavazzi
;
R. Cerbino
;
G. Scita
Ultimo
2017

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.
Chemistry (all); Materials Science (all); Condensed Matter Physics; Mechanics of Materials; Mechanical Engineering
Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)
Settore MED/04 - Patologia Generale
THE ENDOCYTIC AND CYTOSKELETAL MATRIX IN THE PLASTICITY OF TUMOR CELL INVASION AND MIGRATION
Anisotropies and non equilibrium in soft matter: routes to the self assembly of advanced materials
30-gen-2017
http://www.nature.com/nmat/
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/487548
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