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 tools allow such migration to be interactively guided. We present a new bioreactor that harnesses electrotaxis—directed cell migration along electric field gradients—by integrating multiple 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 directing cells to migrate in a complete circle. Our stimulation scheme proves that cells effectively timeaverage electric field cues, helping to elucidate the transduction time scales in electrotaxis. Together, this work represents a fundamentally different platform for controlling cell migration with broad utility across fields.

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