Dynamic self-organization of migrating cells under constraints by spatial confinement and epithelial integrity.

Understanding how migrating cells can establish both dynamic structures and coherent dynamics may provide mechanistic insights to study how living systems acquire complex structures and functions. Recent studies revealed that intercellular contact communication plays a crucial role for establishing cellular dynamic self-organization (DSO) and provided a theoretical model of DSO for migrating solitary cells in a free space. However, to apply those understanding to situations in living organisms, we need to know the role of cell-cell communication for tissue dynamics under spatial confinements and epithelial integrity. Here, we expand the previous numerical studies on DSO to migrating cells subjected spatial confinement and/or epithelial integrity. An epithelial monolayer is simulated by combining the model of cellular DSO and the cellular vertex model in two dimensions for apical integrity. Under confinement to a small space, theoretical models of both solitary and epithelial cells exhibit characteristic coherent dynamics, including apparent swirling. We also find that such coherent dynamics can allow the cells to overcome the strong constraint due to spatial confinement and epithelial integrity. Furthermore, we demonstrate how epithelial cell clusters behave without spatial confinement and find various cluster dynamics, including spinning, migration and elongation.