SCHEEPDOG: Programming Electric Cues to Dynamically Herd Large-Scale Cell Migration

Directed cell migration is critical across biological processes spanning healing to cancer invasion, yet no existing tools allow real-time interactive guidance over such migration. We present a new bioreactor that harnesses electrotaxis—directed cell migration along electric field gradients—by integrating four independent electrodes under computer control to dynamically program electric field patterns, and hence steer cell migration. Using this platform, we programmed and characterized multiple precise, two-dimensional collective migration maneuvers in renal epithelia and primary skin keratinocyte ensembles. First, we demonstrated on-demand, 90-degree collective turning. Next, we developed a universal electrical stimulation scheme capable of programming arbitrary 2D migration maneuvers such as precise angular turns and migration in a complete circle. Our stimulation scheme proves that cells effectively time-average electric field cues, helping to elucidate the transduction timescales in electrotaxis. Together, this work represents an enabling platform for controlling cell migration with broad utility across many cell types. A wide range of cell types across the tree-of-life migrate directionally when exposed to direct current electric fields such as occur endogenously during injury. This process is called “electrotaxis,” and being able to harness and control it would allow new ways to program and control cell and tissue behavior. To demonstrate this, we built SCHEEPDOG—a programmable electro-bioreactor that programs cellular ensembles and tissues to undergo large-scale 2D migration maneuvers.