Influence of proliferation on the motions of epithelial monolayers invading adherent strips

Abstract

Biological systems integrate dynamics at many scales, from molecules, protein complexes and genes, to cells, tissues and organisms. At every step of the way, mechanics, biochemistry and genetics offer complementary approaches to understand these dynamics. At the tissue scale, in vitro monolayers of epithelial cells provide a model to capture the influence of various factors on the motions of the tissue, in order to understand in vivo processes from morphogenesis, cancer progression and tissue remodelling. Ongoing efforts include research aimed at deciphering the roles of the cytoskeleton, of cell-substrate and cell–cell adhesions, and of cell proliferation-the point we investigate here. We show that confined to adherent strips, and on the time scale of a day or two, monolayers move with a characteristic front speed independent of proliferation, but that the motion is accompanied by persistent velocity waves, only in the absence of cell divisions. Here we show that the long-range transmission of physical signals is strongly coupled to cell density and proliferation. We interpret our results from a kinematic and mechanical perspective. Our study provides a framework to understand density-driven mechanisms of collective cell migration.