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Spatial confinement modulates cell velocity in collective migration

Depending on the physiological or pathological conditions under consideration, cells can migrate as large and cohesive epithelial sheets. Whereas most of the previous works suggest that migratory mechanisms are strongly regulated by intercellular contacts, the impact of physical constraints on collective migration remains unclear.

A recent study led by Danahe Mohammed, a Ph.D. student at the time of this study, and Professor Sylvain Gabriele of the University of Mons in Belgium reports that the spatial confinement exerted by neighboring cells modulates the migration velocity of epithelial tissues. This work was published in the June 2019 issue of Nature Â鶹ÒùÔºics.

Gabriele's team reproduced the physiological confinement observed in living tissues in a very controlled way by using microfabrication techniques for generating adhesive microstripes. These in vitro models allow the researchers to confine individual epithelial cells on adhesive tracks with widths varying from five to 20 µm, without making any intercellular adhesions. The research team used epithelial cells harvested from the scale of Central American cichlid Hypsophrys nicaraguensis as a robust primary model of migration.

They report that cells migrating in confined environments slow down and change their three-dimensional morphology, as observed in dense epithelial tissues. Gabriele's team revealed that confined environments reduce the protrusive forces exerted at the cell front and prevent the maturation of focal adhesions at the trailing edge, together leading to less-effective forward-propelling forces. These findings demonstrate that epithelial confinement alone can induce follower-like behaviors and identify substrate adhesive area confinement as a key determinant of cell velocity in collective migration.

The interface between physics, surface chemistry and cell biology once again sheds light on a cellular mechanism that has been poorly understood so far and provides a generic mechanism for the interpretation of collective migration.