UB Biophysicists Discover High-Speed Motility in Cells in Response to Voltage Changes

BUFFALO, N.Y. -- University at Buffalo biophysicists studying the motility of cells have shown that simple cells react in less than a millisecond to changes in membrane voltage, a property scientists have thought was confined to highly specialized cells such as the cochlear outer hair cells responsible for hearing.

In addition to providing new, basic information on how cells function, the finding calls into question the accepted purpose of the so-called "motor protein" prestin, which was thought to be essential for outer-hair-cell motility in the cochlea.

"We have found that cells 'wiggle' at high speed when voltage changes," said Frederick Sachs, Ph.D., UB professor of physiology and biophysics and the study's senior author. "They don't need any special proteins or lipids" to accomplish the movement.

Sachs is director of UB's Center for Single Molecule Biophysics and an authority on cell mechanics. The study appears in the Sept. 27 issue of the journal Nature.

Sachs and colleagues achieved their findings using instruments that can detect movements smaller than the diameter of a hydrogen atom. The measurement technique involves an atomic force microscope that uses a laser to measure the position of a pointed silicon probe, much as a phonograph needle tracks the grooves in a record. These experiments also allowed the researchers, for the first time, to compute the charge that is bound to the inner surface of a cell membrane.

The discovery of this basic property of cells, irrespective of their sophistication, came somewhat serendipitously. Sachs and colleagues had been trying to measure the motion of single ion channels, membrane proteins that function as biological transistors and control cells' voltage. Surprisingly, they found that the membrane itself moved with voltage. Even more surprising, they found that by diluting the concentration of ions in the solution bathing cells, they could reverse the direction of movement.

"When we could change the sign of the response, we knew we were looking at something fundamental," Sachs said.

Knowing how the supporting membrane moves, they now can distinguish the superimposed motion of the ion channels.

"If you are going to study motion changes with voltage of things imbedded in the cell membrane, you need to know the background movement," Sachs said. "If you want to know how an embedded protein is changing shape, you first need to know the background motion."

Finding this common property of cells allows scientists to move on to investigate whether the motility is used by biological systems. "By looking at very simple cells, we may learn more easily how specialized cells work," Sachs said. "If all cells move, we now can ask why nature bothered to make a specialized cell? We think it is to make the cell move faster."

Since cells move with voltage, and movement produces sound waves, Sachs predicts that the brain emits sounds during activity and that recording these sounds may eventually serve as a clinical diagnostic tool, much like electroenchephalograms, or EEGs, are used to look for regions of abnormal activity in the brain.

Ping-Cheng Zhang, Ph.D., and Asbed M. Keleshian, M.D., Ph.D., research scientists in the UB Center for Single Molecule Biophysics, were major contributors to the research.

The study was supported by grants from the National Institutes of Health, the U.S. Army Research Office, the Cell Mechanosensing Project, Japan Science and Technology Corporation and the Ralph Hochstetter Medical Research Fund in honor of Dr. Henry C. and Bertha H. Buswell.