Delayed jamming-induced oscillatory migration patterns of epithelial collectives under long-range confinement.

Collective dynamics of cells in confined geometry regulate several biological processes including cell migration, proliferation, differentiation, and communication. In this work, combining simulation with experimental data, we studied the oscillatory motion of epithelial sheets in smaller areas of confinement, and we linked the monolayer maturation induced-jamming with the wave formation. We showed that epithelial cell populations with delayed jamming properties use the additional time available from this delay to coordinate their movement, generating wave motion in larger areas of confinement compared to control populations. Furthermore, the effects of combining geometric confinement with contact guiding micro-gratings on this wave formation were investigated. We demonstrated that collective migratory oscillations under large geometrical confinement depend on the jamming state of the cell monolayers. The early dynamical state of the experimental results obtained was simulated by self-propelled Voronoi computations, comparing cells with solid-like and fluid-like behavior. Together our model describes the wave formation under confinement and the nodal oscillatory dynamics of the early dynamic stage of the system. Insight Box: Collective behavior of cells in confined spaces impacts biological processes. Through experimental data combined with simulations, the oscillatory motion of epithelial sheets in small areas of confinement was described. A correlation between the level of cell jamming and the formation of waves was detected. Cell populations with delayed jamming presented wave motion in larger confinement areas. The effects of combining geometric confinement with substrate micro-gratings demonstrated that the collective migratory oscillations in large confinement areas rely on the jamming state of cells. The early dynamical state was simulated using self-propelled Voronoi computations that help to understand wave formation under confinement and the nodal oscillatory dynamics of early-stage systems.