SCHEPHERD: A modular, programmable, direct current platform to control cell behavior

Spanning frogs, fish, and humans, direct current (dc) bioelectric cues play critical roles beyond neuromuscular function, such as modulating morphogenesis, immune response, and healing through electrotaxis-electrically directed cell migration. Harnessing this potential requires dedicated, versatile tools. However, standardized, accessible, and reproducible infrastructure capable of dc stimulation remains a challenge. We present SCHEPHERD: a universal, electrobioreactor integrating eight stimulation channels and modular inserts to enable most electrotaxis assays in one device (cells, monolayers, and 3D spheroids) while enabling powerful, expanded capabilities. SCHEPHERD revealed through parameter sweeps that dc fields act like a "steering wheel and gas pedal" for cell migration. We then used live confocal imaging to observe electrically reprogrammed F-actin dynamics. Last, our multipolar inserts generated complex spatial electrical patterns that reorganize engineered tissue dynamics. By substantially improving accessibility through modularity and an open-source, graphically programmed, stand-alone stimulator, we hope that SCHEPHERD can help broaden the community studying these important dc bioelectric phenomena.