Physical Confinement Induces the Transition from Collective to Single Cell Migration

Cell migration, synonymous with cell movement, is closely related to cell movement and refers to the movement of cells after receiving a migration signal or sensing a concentration gradient of certain substances. During the movement, the cells continuously repeat the process of projecting the synapse/pseudopod to the front and then pulling the posterior cell. The cytoskeleton and its binding proteins, as well as the intercellular substance, are the material basis of this process, and there are many substances that make precise adjustments to this process. While single cell migration has been comprehensively investigated in vitro and in vivo, little is known about the collective migration. In this project, we use PDMS and polyacrylamide-based microfluidic platforms to mimic the tissue tracks in human body. Based on our data for A431 carcinoma cells, confining geometries of microfluidic devices exert physical effects on collectively migrating cells and catalyze the transformation from collective to single cell migration under increasing degrees of confinement. Additionally, we also find that E-cadherin overexpression and Myosin IIA inhibition reduce the transformation of collective migration to single cell migration. Finally, we are able to build a pathway elucidating a potential mechanism governing the dissociation of leader cells from collectively migrating cells under the implementation of physical cues. This mechanism for collective cell migration in confinement may provide new approaches to develop cancer therapies and diagnostics