Bioengineering

“What we’re really looking to do is provide the interface between an electronic system—we have excellent ability to design almost anything we want in electronics—and bridge that to the biological system,” says Melosh, an assistant professor of materials science and engineering. “We’ve, in effect, been able to turn on local protein activity by using an electrical field. We can start giving proteins certain chemical signals that will direct specific behaviors.”

Electronic control of protein activity could allow Melosh and his research group to tap directly into the molecular mechanisms that govern most of the body’s fundamental functions—for example, the movement of individual cells or entire muscles. These processes start and stop based on the movement and physical interaction of proteins, ions, and molecules. Those, in turn, often depend on electrical charge. Melosh’s emerging techniques use electronics to control those processes by manipulating the ambient electrochemical conditions.

The body electric
Electrochemical processes in the body involve one of two mechanisms: Either molecules redistribute electrons and therefore charges (redox reactions), or they are pushed around by electric fields based on their inherent charge (non-redox reactions). While other researchers have long tinkered with redox reactions, Melosh’s small group has focused on manipulating the non-redox ones, in large part because they are much more common. In a paper initially published on the Web Sept 18th in the journal Soft Matter, the group demonstrated the first direct electrical manipulation of a non-redox process.

“We’ve had no way to control those kind of non-redox processes with electrochemistry or an electrical interface before,” he says. “This is the first time we’ve been able to show that you can control these non-redox active proteins using electric fields.” Specifically, Melosh, graduate student Ian Wong, and medical postdoctoral researcher Matthew Footer wanted to see if they could, with precise electronic control, make proteins called actins “polymerize” into long, thin filaments. Actin carries a strong negative charge, but when it meets up with positively charged magnesium ions, it can braid into helical filaments (like DNA strands). When actin does that in the body it plays a key role in cell movement, cell shape, and muscle contraction.

To make it happen in the lab, they devised an experiment in which they put loose globs of actin into a solution with a relative dearth of magnesium ions. The lack of magnesium ensured that the filament formation wouldn’t occur spontaneously. The researchers would need to intervene in the proper way for anything to happen.

That intervention came in the form of placing a pair of titanium electrodes into the solution spaced 50 millionths of a meter apart. The idea was simple; when the electrodes were turned on, they would attract and concentrate the charged materials to such a degree that the reaction would begin and filaments would start to form.

At first the researchers applied a direct current, meaning that each electrode retained a positive or negative polarity the whole time. In this scheme, the actin never formed filaments, likely because the actin was attracted to the positive electrode while the magnesium migrated to the negative one.

But then the researchers applied an alternating current, meaning that 100 times a second the electrodes would switch their polarity. This caused the actin and magnesium to mix quite a bit as they shuttled back and forth between the electrodes. Within half an hour filaments had begun to form on the surface of each electrode (where the fields were strongest). After two hours the electrodes looked like they could use a haircut. The addition of an actin filament bundling agent and an actin-specific fluorescent tag made the filaments dramatically visible under a microscope. By spacing the electrodes closer together, they were able to make the reaction occur in minutes.

A proof of concept
“It’s an exciting reaction in that you can see it grow under controlled conditions,” Melosh says. “But the more important thing is that in general this is a proof of concept that now we can take almost any of the non-redox active proteins that have some interesting activity and have some level of control of it electronically using this effect.”

Melosh is quick to point out that this control cannot be directly translated into the body, which does not have the artificially low concentrations of ions his group used in the experiment. At least for now the applications of the work would be in benchtop biochemical research rather than direct control of physiological processes in live beings. Melosh has naturally begun to speculate on where electronic control of proteins could lead.

“You could imagine that if you could control the synthesis proteins directly in these schemes, you could start locally producing proteins of interest,” he says. “One interesting idea would be producing neurotransmitters at one particular spot. You could release the neurotransmitters and create a signal right when and where it’s needed, creating an artificial synapse.”

Meanwhile, a potential use for artificially grown actin filaments, for example, could be to develop programmable nanoscale circuits.

“You could have circuits where you have the electrode contacts there but no nanowires between them,” Melosh says. “This technique could enable you to grow an actin nanowire from one contact to the other controllably.”

February 2007