Biomedical researchers at Princeton University have developed a device that remotely controls the movement of living cells by manipulating electric fields to mimic those found in the body during healing. The device, called the Spatiotemporal Cellular HErding with Electrochemical Potentials to Dynamically Orient Galvanotaxis (SCHEEPDOG), could open new possibilities for tissue engineering, including approaches wound healing, repairing blood vessels and sculpting tissues.
Scientists have long known that naturally occurring electrochemical signals within the body influence the movement, growth and development of cells—a phenomenon known as electrotaxis. These behaviors are not nearly as well understood as chemotaxis, in which cells respond to chemical concentrations. One reason electrotaxis remains relatively unexamined is the lack of accessible tools to monitor cells’ responses to electric fields.
The new device, assembled from inexpensive and readily available parts, lets researchers manipulate and measure cultured cells’ movements reliably and repeatably. SCHEEPDOG contains two pairs of electrodes that generate electric fields along horizontal and vertical axes, recording probes that measure voltages and a protective barrier that keeps the cells isolated from the electrodes’ chemical byproducts. The voltage level in the electrodes is similar to that of an AA battery concentrated over the centimeter-wide chamber containing the cells.
“It’s kind of like an Etch A Sketch,” says Tom Zajdel, a researcher at Princeton. “We’ve got the horizontal and the vertical knobs, and we can get the cells to trace out arbitrary trajectories in the whole 2D space just by using those two knobs.”
The team tested SCHEEPDOG using mammalian skin cells and epithelial cells from the lining of the kidney, which are often used to study cells’ collective movements. They found that the cells time-averaged signals generated along the two axes over periods of about 20 sec.: Turning on the vertical electric field for 15 sec. and the horizontal field for 5 sec., for instance, would cause the cells to migrate more vertically than horizontally.
The team is now using the device on different cell types and situations. One group of experiments, for example, examined how cells stuck to other cells (adhesion) are affected by cell movements. This could be important for understanding and possible controlling skin, blood vessel and nerve regeneration.
Applying engineering principles to understand and control electrotaxis will deepen understanding of its role not only in cell movement, but also in growth and differentiation. Although today’s cutting-edge tissue-regeneration techniques usually involve pre-patterning new tissues, it might be a better approach to sculpt tissues with electric fields.
Editor's Note: Click here for some microscopic views of SCHEEPDOG in action.