Laser seeks out and zaps cell proteins.

Laser seeks out and zaps cell proteins

A cell resembles a walled city, barricaded by a double layer of fatty molecules called lipids. Communication with the outside world is critical to the cell's development and survival, so information about what's happening on each side of the cell wall is mediated by specialized proteins. Scientists usually study the function of these proteins by introducing mutations into the gene for one protein and studying the effect on cell function. Now a researcher at Harvard Medical School in Boston has demonstrated he can do these studies without genetic manipulation by zapping specific proteins with a laser.

The method, called chromophore-assisted laser inactivation, involves attaching a laser-absorbing molecule (a chromophore) to an antibody that will selectively attach itself to one kind of protein on the cell surface. A series of short (10.sup.-8.second) pulses of laser light -- of a wavelength absorbed by the chromophore but not by the cell -- is focused on the tissue after it has been exposed to the antibody. In a trial with red blood cells, Daniel Jay found that the heat absorbed by the chromophore is enough to disrupt the cell surface protein bound to the chromophore-antibody combination, but not enough to affect other proteins or the cell itself, he reports in the August PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (Vol.85, No.15).

Jay calculates that the technique works because the heat radiated by the chromophore raises the temperature directly around it 130[deg.]C, but the rapid dissipation of heat means that the temperature a few hundred atomic widths away rises only about 2[deg.]C, he says.

The technique offers an advantage over genetic approaches because it allows scientists to inactivate one type of protein in a single cell within an organism by focusing the laser on that cell only, Jay says. Moreover, the depletion of proteins is short-lived, because the cell will produce replacement proteins, he adds.

These two properties make the method valuable for studying protein-mediated events that happen only at one place and time, such as some of the cell changes that occur in a developing organism, Jay says. One area of interest for Jay is the study of how neurons know where to go to "wire up" the developing brain. Cell surface proteins are important in this process, and the laser inactivation technique may reveal more about the specific proteins that guide neurons and how they do it, he says.

Researchers also can guide a chromophore to a cell surface protein by attaching it to an enzyme, Jay says.