Applying Swarm Engineering to Control Collective Cell Dynamics

Multicellular life is driven by collective cell migration spanning morphogenesis, growth, wound healing, and even cancer invasion.  Our group seeks to better understand such collective behaviors in living tissues in order that we can learn to control them, much as a shepherd and sheepdog herd sheep. Drawing on biophysics, swarm theory, cell biology, and engineering, we are developing new tools to manipulate collective cell dynamics. Here, we will explore two such approaches—'Outside-In’ and ‘Inside-Out’ control. In the former case, we steer epithelial tissue collective migration and growth in real-time during using programmable electric fields (electrotaxis). Crucially, global commands (e.g. ‘Move Left’) are locally interpreted by subdomains of cells within the larger tissue, making precise, complex control feasible. We are working to refine both the instrumentation and our understanding of what electrotaxis can, and cannot do, with regards to controlling or ‘sculpting’ complex tissues. 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 behaviors from within a tissue. Together, our swarm control approaches offer new tools to interactively control the behavior of living tissues.