Moving single cells
Opsins can do more than “see” in the way we typically think of seeing. In fact, they can activate cells to respond to their environments.
Light sources (rectangles) attract modified cells.
N. Gautam, PhD, professor of anesthesiology and genetics, and postdoctoral research associate Ajith Karunarathne, PhD, are exploring how light can cause opsins to behave in cells. When they inserted opsin proteins, which are G protein-coupled receptors (GPCRs), into cells, they found that by shining light on the cells, they could activate specific areas. This bit of genetic engineering permits opsins to activate other types of cells.
“Some of these opsins have properties that we thought might allow us to localize the signaling activity in a cell to a particular location in the cell,” says Gautam. “So we began experimenting, and we found that we could, in fact, localize the signaling to one side of the cell or another. A great deal of cell behavior results from signaling where the cell will sense something on its right, for example, and then move toward that substance, or move away from it.”
An immune cell, for instance, that receives a signal and senses a bacterial infection or inflammation, will travel in the direction of the bacteria or the inflammatory molecules. When Gautam and Karunarathne inserted opsins into immune cells, the cells moved toward a light beam.
“We can use light as a kind of ‘on-off’ switch to control cell behavior,” says Gautam. “Much of the way cells behave is due to their ability to sense signals in the environment. In our experiments, the cells sense the presence of light.”
In neurons, they have used light to coax the cells into growing new branches called neurites. They are planning similar things in heart cells and in pancreatic cells.
The goal with the heart cells would be to use light to slow down, or speed up, the rate at which the cells pulse. In pancreatic cells, they want to use light to get the cells to secrete insulin.
“We believe that with these techniques, it’s likely that any process that can be controlled by signaling from GPCRs can also be controlled by light,” Gautam says.
Although Gautam believes that inserting opsins into cells has immense therapeutic potential, he says it will be a while before the strategy is ready for clinical use. For one thing, it will require gene therapy in order to introduce the light-sensitive proteins into specific cell populations. For another, it will require a way to introduce light into cells deep inside the body, perhaps using micro-light emitting devices (LEDs).
While his laboratory is working on ideas to take this strategy from the culture dish into whole animals, they also are creating a library of several different opsin proteins capable of controlling cell behavior.
“As we move forward, one of our goals is to continue testing multiple opsins from different organisms to learn which ones work best,” he says.