In 1849, a German physiologist named Emil du Bois-Reymond cut his arm and measured the electricity flowing across the wound. To his surprise, he found that the skin there generated a powerful magnetic field. Ever since, researchers have probed how this self-generated electricity moves cells in a process essential to wound healing and embryonic development. Now, a new technique that “herds” living cells like sheep might help unravel why—and how—cells respond to electrical currents.
Researchers know surprisingly little about this “science fiction” process, known as electrotaxis, says Daniel Cohen, a biological engineer at Princeton University. For example, they know that electric gradients help protect surfaces such as the gut from invaders by creating a repellent charge, and some immune cells function better in the presence of magnetic fields. One thing is certain: Cells seem to respond actively to those fields, restructuring their inner skeletons to move closer to, or farther away from, the source.
But until now, scientists studying electrotaxis have only been able to move cells back and forth. Lab setups are simple, with positive and negative magnetic poles that pull cells toward one end of a dish or the other. To study the phenomenon in depth, Cohen and colleagues built a system that includes two pairs of electrodes, one on a horizontal axis and one on a vertical axis. Spatiotemporal Cellular Herding with Electrochemical Potentials to Dynamically Orient Galvanotaxis, or SCHEEPDOG, as they call it, allows them to herd cells in two dimensions.
The researchers were able to move skin cells in a dish in any direction at multiple speeds, even forcing them to perform complex maneuvers like 90° turns or circles (see video, above). Cohen, who published the setup last month on the preprint server bioRxiv, describes SCHEEPDOG as “dirt cheap” and says scientists can assemble a similar setup in less than 1 hour.
That excites cell biologist Ann Rajnicek of the University of Aberdeen. She says the new tool could allow scientists to watch in real time as cells detect signals and restructure themselves to move. She’d like to see the system tested with different cell types, such as neurons or immune cells, which would likely move differently than the sheets of skin cells. Indeed, Cohen’s team found that one of their two skin cell types took longer to reorient themselves, suggesting they might use different mechanisms.
SCHEEPDOG could also lead to therapeutic applications, particularly in wound healing, where it could help build biological Band-Aids to cover a lesion. “The technology seems very exciting,” says Abigail Koppes, a biological and chemical engineer at Northeastern University, who studies bioelectronics.
Koppes is especially intrigued given emerging findings about the body’s natural electrical fields. A November 2019 paper in eNeuro, for example, mapped for the first time an electrical field along the division between the brain’s two hemispheres. When researchers injected neural stem cells into slices of mouse brain, the cells moved along the direction of the field. But when they applied an external electrical stimulus to counteract the natural field, they could direct the cells where they wanted them to go.
Knowing how cells respond to the body’s electricity—and how to counteract natural fields with external currents—could help improve stem cell therapies or efforts to treat diseases such as Parkinson’s by injecting dopamine-producing cells into the brain. “That’s where SCHEEPDOG could come in,” Koppes says.
Cohen says the new approach might need more fine tuning in order to move different types of cells, or to push them in three dimensions for other applications—like building lab-grown organs. But in the shorter term, creating such an electric field inside a wound might help accelerate the body’s natural healing processes, and Cohen says his team is working on miniaturizing the system so that it could be implanted into animal models to do just that.