Tiny Sheep: UC Berkeley Researchers Use Electricity to Herd Cells and, Potentially, Speed Up Healing

Since the late 1700s, scientists have known that the water, salt, and ions that flow through the body conduct electricity, but its significance remained a mystery. The concept of “bioelectricity” inspired the story of Frankenstein and had for a while been of more interest to pop culture than to science. But in the 1800s, physiologist Emil Du Bois Reymond discovered that the electric field of cells changed during an injury. By cutting his own thumb and measuring the electric field, Reymond revealed that there is a spike in electric current around an injury site.

Galvanotaxis, a process that uses electric currents to direct cells, is rarely used in the field of bioengineering. But recently, a group of researchers used galvanotaxis to herd a group of cells in different directions. In the past, the process had been used to move single cells, but this was the first time electric currents had engineered tissue swarming. The discovery could help speed up the healing of a wound, reduce scarring, grow organs, and guide cancer research.

By using electric currents, researchers are studying how epithelial cells, which sheath the skin and other organs, respond to electric fields and move in unison. “It's clear that these sheaths perform fairly complex tasks, but it's not really clear how they coordinate with each other entirely,” says Michel Maharbiz, an associate professor of electrical engineering and computer sciences at UC Berkeley.

Daniel Cohen, a doctorate student in the UC Berkeley-UC San Francisco Joint Graduate Program in Bioengineering, shows what this coordination looks like in a photo of epithelial cells. He points out the nucleus, a blue dot in the center of a cell, which is about one-fifth the width of a human hair. A red outline surrounds each of the polygonal-shaped cells, indicating where they are “chemically holding hands,” Cohen says. Epithelial cells are highly social and like to create a community with their neighbors. During an injury, the epithelial cells are the first to respond to the wound site. The cells heal the wound by migrating. They see a cut as a schism in their group. “On a daily basis, these guys are just following a couple of simple rules: They hate being alone and they hate free space — so they don't like anywhere where there are no cells,” says Cohen.

Which addresses a question scientists have asked for more than a century: Can you use electric fields to guide cells and make an injury heal faster? Drawing inspiration from the migratory patterns of sand, birds, fish, and sheep, Cohen wondered if he could use electric currents to engineer the swarming process in cells. He wanted to act as a shepherd, herding the cells with electric inputs. “Sheepdogs and shepherds have the ability to take a humungous number of sheep and with very few inputs — a couple of dogs — they can get the sheep to go wherever they want and to form different shapes,” says Cohen.

To create the swarming effect, Cohen had to create a wound, or a reasonable facsimile anyway: a series of tubes carrying salt solutions to cells in a Petri dish. A stencil made out of medical tape lined the bottom of the dish. Once Cohen applied an electric charge, thousands of cells swarmed together. The cells adapted to the various shapes of the mold, which included a triceratops and a Cal bear. These molds were a way for Cohen to make sure the cells could be moved to fit the different shapes of a wound. Cohen soon became an adept micro-shepherd, using currents to direct the cells right or left and to make a U-turn. He was surprised that he didn't have to micromanage each of the cells. “We're able to show these complex behaviors like having an entire population turn around, left or right without actually telling it how to do that. It figures it out on its own,” says Cohen. The process proved it would only take a simple nudge to get epithelial cells moving in unison; the researcher gives them a jolt and the cells take care of the rest.

Although it wasn't explored during the study, Cohen also hopes to look at the way cancer metastasizes through the lens of swarm dynamics. Cancer cells penetrate the noncancerous tissue around it by breaking down the connection between healthy cells. Metastasis, according to the researchers, demonstrates the reverse of swarming behavior — separating the healthy tissue into individual cells, which allows cancer to enter the bloodstream. “[Cancer cells] take a tissue with a nice collective behavior that acts as a community and they break the communal rules and sneak out,” says Cohen. Studying the reverse swarming process could help cancer researchers control metastasis.

Cohen and Maharbiz plan to apply what they have learned in their study to create a smart bandage: a grid of electrodes that hovers over an injury to measure the electric field. Once the bandage tests the electrical properties, it could then stimulate currents back into the wound to expedite healing. Although the smart bandage is still in development, Maharbiz also hopes that it could be used to strengthen scar tissue. “It's fairly well-known that after something like an abdominal incision you're given during surgery, you recover and your wound heals, but it's never quite as strong as it was when you were completely uncut,” says Maharbiz. If it proves useful, Cohen hopes that the smart bandage is something that will be accessible to the public. Kids will love the triceratops.

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