Collective migration and topological phase transitions in confluent epithelia

Abstract: Collective epithelial migration leverages on topological rearrangements of the intercellular junctions, which allow cells to intercalate without loosing confluency. In silico studies have provided a clear indication that this process could occur via a two-step phase transition, where a hierarchy of topological excitations progressively transforms an epithelial layer from a crystalline solid to an isotropic liquid, via an intermediate hexatic liquid crystal phase. Yet, the fundamental mechanism behind this process and its implications for collective cell behavior are presently unknown. In this article, we show that the onset of collective cell migration in cell-resolved models of epithelial layers takes place via an activity-driven melting transition, characterized by an exponentially-divergent correlation length across the solid/hexatic phase boundary. Using a combination of numerical simulations and Renormalization Group analysis, we show that the availability of topologically distinct rearrangements - known as T1 and T2 processes - and of a non-thermal route to melting, renders the transition significantly more versatile and tunable than in two-dimensional passive matter. Specifically, the relative frequency of T1 and T2 processes and of the "bare" stiffness of the cell layer affect the divergence of positional correlations within a well-defined spectrum of critical behaviors. Suppressing T1 processes, changes the nature of the transition by preventing collective migration in favor of a cellular analog of surface sublimation.