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\u00a0<\/strong><\/p>\n Epithelial cells collectively migrate in the human body in a compact and cohesive monolayer. This characteristic is necessary to ensure the barrier role of epithelia and mainly relies on intercellular adhesions. In physiological and pathological conditions, such as metastasis formation, there is evidence that not only single cells, but groups of polarized cell clusters detach from the primary tumor lesion and migrate in a high directional persistence mode. However, how is the migratory efficiency of these cell cohorts modulated by their size and intercellular adhesions remains unclear.<\/p>\n To answer this question, we designed an\u00a0experimental platform based on protein micropatterning, with which we formed\u00a0standardized cell cohorts of varying\u00a0complexities. We formed fibronectin microstripes\u00a0of different widths (15, 30 and 45 \u00b5m) to impose biochemical boundary\u00a0conditions. By modulating the microstripe\u00a0width, we increased gradually the\u00a0number of neighboring cells, and thus lateral cell-cell interactions. We used\u00a015 \u00b5m wide microstripes for studying the migration of\u00a0single epithelial cells\u00a0and trains of cells connected to each other with axial intercellular adhesions,\u00a0whereas 30 \u00b5m and 45 \u00b5m wide microstripes were used to observe\u00a0the migration of\u00a0epithelial cohorts with one or two sides of lateral adhesive contacts,\u00a0respectively.<\/p>\n Our findings show that trains of cells on\u00a015 \u00b5m wide microstripes exhibit a similar migration speed than individual\u00a0cells, regardless the train length.\u00a0Interestingly, the establishment of lateral\u00a0adhesive interactions between neighbouring cells slows down drastically the\u00a0migration speed of wider epithelial cohorts.\u00a0Our results highlight therefore\u00a0the importance of lateral adhesive interactions in fine-tuning epithelial\u00a0migration. To confirm these observations, we used ethylene\u00a0glycol tetraacetic\u00a0acid (EGTA), a chelating agent, to break intercellular adhesive interactions by\u00a0complexing calcium cations implied in cadherin junctions. Our\u00a0results show that\u00a0EGTA-treated cells of wide cohorts (30 and 45 \u00b5m wide) are significantly\u00a0faster, whereas EGTA-treated cells in trains of cells exhibit similar\u00a0migration\u00a0speed, confirming the key role of cadherin-based intercellular junctions in\u00a0collective migration dynamics.<\/p>\n To gain further insight into the mechanism\u00a0that controls the modulation speed in collective epithelial systems, we\u00a0performed traction force microscopy (TFM)\u00a0experiments on train of cells (15 \u00b5m\u00a0wide) and epithelial clusters of 30 and 45 \u00b5m wide. We found that the total\u00a0contractile energy exerted on the substrate increases\u00a0significantly with the\u00a0cohort widening. Interestingly, the axial contractile stress remains constant,\u00a0whereas the radial contractile stress increases significantly with the\u00a0cohort\u00a0widening, demonstrating that a large part of the contractile energy in large\u00a0epithelial clusters is not affected to the direction of migration. We then\u00a0quantified\u00a0the internal stress distribution with monolayer stress microscopy\u00a0(MSM). While the axial internal stress component is constant across the\u00a0different clusters, the radial\u00a0internal stress component increases\u00a0significantly, suggesting that the internal stress exerted between neighbours increases\u00a0with the establishment of lateral adhesive\u00a0interactions. Altogether, this\u00a0multiscale study of epithelial systems allows to explain mechanically why small\u00a0groups of cells can migrate more efficiently than large\u00a0assemblies.<\/p>\n \u00a0 Epithelial cells collectively migrate in the human body in a compact and cohesive monolayer. This characteristic is necessary to ensure the barrier role of epithelia and mainly relies on intercellular adhesions. In physiological and pathological conditions, such as metastasis formation, there is evidence that not only single cells, but groups of polarized cell […]<\/p>\n","protected":false},"author":15,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[],"tags":[],"class_list":["post-615","post","type-post","status-publish","format-standard","hentry"],"yoast_head":"\n<\/div>\n","protected":false},"excerpt":{"rendered":"