Spatially patterned collective cell motion within large tissue sheets changes local mechanics

Collective cell migration is a critical biophysical process that underlies development, healing, and cancer invasion. Understanding and controlling large scale collective migration is therefore of great interest. Importantly, natural collective systems in the body exhibit complex, non-uniform patterns of collective behavior, such as a small group of cells that moves within a larger tissue. However, it has been difficult to replicate or control such local patterns within a larger continuum-like tissue. Here, we show new data of inducing precise, local patterns of migration within larger cellular communities using electrotaxis—directed cell migration in response to ionic currents—and how information from these local patterns propagates throughout the broader community. Our modifications allow us to precisely shape 2D heterogenous electric fields to drive complex cell motion within larger tissues such as converging, diverging, traffic-jam, and multi-pole migration patterns. Sculpting fields at this scale allows us to examine different biophysical properties of the tissues. Here, we discuss the collective response and relaxation of a confluent 2D epithelial layer comprised of primary-mouse keratinocytes of varying cell-cell coupling strengths using the simplest of heterogenous field shapes: a 1d “delta” function—a strong localized electric field which decays rapidly with distance from its center. Preliminary findings suggest that cell migration speeds peak where the electric field is strongest; however, the directed migratory response extends to regions where the field strength falls beneath the electrotactic response threshold of the cells indicating the importance of cell-cell coupling. Furthermore, after we switch off electrical stimulation, the displaced zone of the tissue retracts with dynamics that depend on the cell-cell coupling. This relaxation provides preliminary insights into how cell-cell coupling regulates the viscoelastic properties of an epithelial tissue which will be discussed here.