June 2001

From University of North Carolina at Chapel Hill

Using lasers, biologists succeed in getting cells to change course

CHAPEL HILL - Most people probably think that most cells in the body -- not counting blood cells -- stay in one place their entire lives just as whole plants do, but nothing could be further from the truth.

These microscopic living structures move a little or a lot, healing wounds, developing embryos, scouting and attacking disease-causing invaders and, sometimes, spreading cancer. As a result, the mechanics and chemistry of how cells get themselves from one place to another fascinates researchers around the world.

Now, using a beam of laser light only a few microns in diameter, University of North Carolina at Chapel Hill scientists have succeeded for the first time in getting such light to alter the course of a moving cell. They have accomplished that by having the laser create active proteins from what are called "caged" proteins that they introduced into the cell.

A report on the research appears in the May 28 issue of the Journal of Cell Biology.

The work has begun attracting attention from other scientists internationally.

"We put caging groups on particular amino acids of the protein we were interested in inside single cells and that makes the proteins less active," said Dr. Kenneth A. Jacobson, professor of cell and developmental biology at the UNC School of Medicine. "Then we directed the laser beam into part of the cells to break the bond between the caging group and the amino acid so that the protein became active again. Afterward, depending on where we shined the light, cells turned by as much as 90 degrees."

Their experiments might be likened to putting the breaks on one rear wheel of a car so that the car would tend to pull to one side or another, Jacobson said.

Besides Jacobson, UNC authors are Drs. Partha Roy, a postdoctoral fellow soon to join the research faculty, and Zenon Rajfur, research associate. Drs. Gerard Marriott and Leslie Loew of the universities of Wisconsin and Connecticut, respectively, and David Jones of UNC, now a medical student at Wake Forest University, also participated.

The team carried out their work on cells taken from fish scales that are somewhat comparable to human skin cells, Roy said.

"The laser technique we used is novel and powerful because it allows us to actually manipulate proteins in specific places inside cells and do it instantaneously," he said. "That's a huge advantage over conventional genetic approaches, which take a lot of time and can be compensated for by cells making other proteins that nullify the original genetic manipulation."

Light-directed disruption studies promise to teach scientists much about cell movement and behavior, Roy said.

"We think this opens a lot of possibilities for learning what many signaling molecules do inside cells," he said. "If you can understand the behavior of an internal protein, then you can make inhibitors or promoters that have implications for drug discovery. In some cases, such as formation of new blood vessels in the treatment of coronary artery disease, you might want to speed up cell movement. On the other hand, you'd want to stop movement of cancer cells." Through a project with UNC's Center for Inflammatory Disorders, Jacobson's laboratory is now applying the photo-release technique to a major puzzle -- how blood cells can migrate through layers of other cells to sites of infection, Jacobson said.

Muscle physiologists studying calcium developed the laser method to uncage compounds some 10 years ago, he said. The UNC researchers also are developing a promising complementary technique for inactivating specific molecules responsible for making cells move and stick together. "No one had used the laser technique to manipulate protein levels in single, living cells before, and that's why this work is attracting a fair amount of attention from other scientists," the biologist said. "It has many possibilities."

Note: Jacobson and Roy can be reached at 919-966-3855, 966-5703 or via frap@med.unc.edu

By DAVID WILLIAMSON
UNC News Services












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