Cellular herding: learning from swarming dynamics to experimentally control collective cell migration

Multicellular life is driven by collective cell migration spanning morphogenesis, growth, wound healing, and even cancer invasion. Our lab works to interactively manipulate collective cell migration in living tissues, akin to how a shepherd herds sheep. Our first approach relies on ‘Outside-In’ perturbations to direct epithelial collective migration in real-time by exposing cells to programmable electric fields (electrotaxis). Crucially, we have shown that collective migration patterns within a tissue will track even complex 2D field commands (e.g. diverging fields)—a fact that we are exploiting to interactively ‘sculpt’ living tissues via collective migration control. In parallel, we have developed an ‘Inside-Out’ swarm control approach based on introducing ‘cellular mimics’--3D microstructures mimicking the geometry and cadherin presentation of native cell-cell junctions—to tissues in order to recapitulate cell-cell recognition and adhesion between a living tissue and a cellular mimic. By linking into the endogenous coupling network (cell-cell adhesion), these cellular mimics are allowing us to manipulate and program collective cell migration from within a tissue. Together, our swarm control approaches offer new tools to interactively control the behavior of living tissues.