Fabio Giavazzi — Università degli Studi di Milano #
Reawakening of Motility and Flocking in Jammed Epithelia #
Dynamics of epithelial monolayers has recently been interpreted in terms of a jamming or rigidity transition [1,2]. How cells control the proximity to that transition is, however, unknown. Here we show that elevation of the endocytic protein RAB5A, frequently hijacked by different epithelial-like tumors to promote their dissemination, is sufficient to induce large-scale, coordinated motility and flocking in otherwise kinetically-arrested monolayers. Our findings [3] suggest that the increased fluctuations and reawakening of motility are the result of globally enhanced endosomal trafficking and macropinocytotic internalization. These variations lead to an increase in junctional tension and traction forces exerted on the substrate and promote the extension of persistent cell protrusions which align with local velocity. To rationalize our findings, we propose a simple model where, in addition to cell-cell adhesion and cortical tension, we consider an active reorientation mechanism for the velocity of self-propelled cells. The model explains the observed reawakening of RAB5A motility in terms of a combination of large-scale directed migration and a local unjamming [3]. These changes in multicellular dynamics allow collectives to migrate under physical constraints and may be exploited by tumors for interstitial dissemination.
References:
[1] T. Angelini et al., PNAS 108 (12), 4714 (2011)
[2] JA. Park et al., Nature Materials 14, 1040 (2015)
[3] C. Malinverno et al, Nature Materials, Advance Online Publication (2017)