Feeling Proteins Wiggle

There's a new way to watch proteins shimmy and dance as they carry out their biological tasks. Researchers traditionally follow these shape changes spectroscopically, deducing them from changes in the molecules' ability to absorb particular wavelengths of light. But in the current Proceedings of the National Academy of Sciences, a group in Israel reports taking a more direct approach: planting the tip of an ultrafine glass fiber on top of the protein and actually feeling it move.

The researchers--Aaron Lewis, Mordechai Sheves, Michael Ottolenghi, and their colleagues at Hebrew University in Jerusalem and the Weizmann Institute for Science in Rehovot, Israel--zeroed in on bacteriorhodopsin (bR), a protein found in the membranes of certain bacteria, where it responds to light by changing shape and pumping protons across the membrane. To sense these shape changes in a new way, the group used a variant of atomic force microscopy, a technique in which an ultrafine probe is scanned across a surface, sensing its atom-scale bumps and depressions to make an image. Lewis and his colleagues, however, kept the ultrafine probe in one place, poised atop a thin film of bR-filled membranes. In response to pulses of laser light, the proteins changed shape and then relaxed again, in a matter of milliseconds. At the same time, a second laser sensed a minuscule displacement of the probe tip.

The displacement not only showed that the technique worked, says Sheves; it also revealed stages of the protein's shape change that researchers have never reported before. These "spectroscopically silent" motions, says Sheves, point to a new model for the initial responses of the protein to light.

Sheves expects the technique to deliver similar insights into the contortions of other molecules. "It gives you a new direct probe to look at conformational changes in proteins," says Sheves. Robert Glaeser of the University of California, Berkeley, agrees, saying the work could "tell us more about how [motion] plays a role in proteins." But he thinks the work still needs some "reality checks." For one thing, while the researchers know the tip moved, they didn't convert the laser signal into an actual distance.