“In malaria, our first measurements indicate that the membrane stiffens as the parasite ages inside the cell,” says Popescu. “In fact, the cell membrane behaves much like a guitar string. The tighter or stiffer it is, the higher the pitch produced. So, our technique can be regarded as an incredibly sensitive microphone.” In the long term, he says, this kind of optical imaging may have clinical applications: it could yield a way to help reverse such diseases.
Meanwhile, a separate research group in the Spectroscopy Lab, led by postdoctoral associate Christopher Fang-Yen, is using optical interferometry to watch the activity of individual neurons. With this technique, Fang-Yen was able to detect small twitches of a few nanometers in nerve fibers and single neurons during an action potential, or electrical impulse. “Many researchers have observed a transient swelling in nerves during the action potential,” says Fang-Yen. “We’re interested in imaging these motions to detect signaling between neurons.”
Illuminating the mechanical changes in activated neurons may provide a new way of probing the activity of neural circuits, particularly for studies of learning and memory. Current optical imaging techniques for neurons use fluorescent markers, or dyes, that stain for things like calcium ions, an indirect measure of electrical activity. However, Fang-Yen says fluorescence methods are marred by photobleaching, phototoxicity, and slow time scales. The optical technique developed by the Spectroscopy Lab creates nanometer-scale images in less than a millisecond, and it’s not subject to photobleaching or phototoxicity.
John Sedat, professor of biochemistry at the University of California, in San Francisco, sees this optical imaging technique as a new perspective in an evolving field. “There’s a kind of miniature revolution taking place in microscopy,” he says. “This is an example of physics people coming into biology and bringing in a lot of new ways of seeing things.”