It's well known that high doses of aspirin can cause ulcers and temporary deafness, but the biochemical mechanism responsible for these phenomena has never been deciphered.
New research from Rice University offers clues, showing for the first time how salicylate -- an active metabolite of aspirin -- weakens lipid membranes. Researchers believe these mechanical changes disrupt the lining of the stomach, which functions to protect underlying tissue from the acidic contents of the gut. By a similar mechanism, the changes may result in aspirin-related deafness by interfering with the proper function of prestin, a transmembrane protein that's critical for mammalian hearing.
The study appears in the September issue of Biophysical Journal.
"Our studies found that membranes exposed to physiological concentrations of salicylate were thinner, more permeable, easier to bend and more likely to rupture," said study co-author Robert Raphael, the T.N. Law Assistant Professor of Bioengineering.
All cells are surrounded by membranes, ultrathin barriers of fatty acids that are just a few nanometers thick. Membranes act like a skin, sealing off the inner machinery of the cell from the outside world. About 40 percent of human proteins are "transmembrane" proteins, molecules that stick through the membrane like a needle through a cloth.
First identified five years ago, prestin is a transmembrane protein found in the inner ear. A motor protein, prestin is thought to act like a piezocrystal, converting electrical signals into mechanical motion. In the outer hair cells of the cochlea, prestin acts as a molecular motor, causing the cells to move rhythmically and amplify the sounds we hear.
"If you change the mechanical properties of the membrane, you will likely affect the biophysical processes that take place there, including those that are mediated by membrane proteins like prestin," Raphael said.