The hair bundle, the mechanosensitive organelle of the hair cells of the inner ear, shows evidence of a remarkable battle between evolution and physical limitations. The hair bundle is a cluster of linked, finger- like projections, the stereocilia, emerging from the cell's apical surface. Each stereocilium is composed of a dense actin core surrounded by membrane highly decorated with a collection of charged glycoproteins, the glycocalyx. When the ear is exposed to sound, the fluid of the inner ear moves at the frequency of the sound. As the hair bundle is driven back and forth by the motion of the fluid, the mechanotransduction channels at the tips of the stereocilia are pulled open and sound is transduced. To enable us to hear high-frequency sounds, up to 20 kHz, the hair cells must physically oscillate and amplify at these frequencies, fending off dissipative viscous drag at low Reynolds number, and warding off dissipative forces from within the hair bundle. What kind of energy source can power a movement of tens of nanometers, 20,000 times per second, and further, how can such a movement be accomplished continuously for more than 80 years without harming the cellular structures and causing hearing loss? The present studies pursue two distinct lines of research addressing these physical and physiological challenges. First, using quantitative measurements of charge and force, I will investigate the effects of the electrostatic forces of the stereociliary glycocalyx on the physical properties of friction and adhesion in the hair bundle. Then, by developing a permeabilized hair-bundle preparation, I will test the idea that the Ca2+ gradient across the stereociliary membrane is the energy source of the active process of the hair cell at high frequencies. Each of these projects addresses open questions in the field of hair-cell research, questions of both a physical and physiological nature, whose answers are likely to shed light on the devastating phenomenon of use-induced hearing loss that affects approximately one-tenth of the American population. Relevance: Approximately ten percent of Americans suffer from age-dependent and noise-induced hearing loss. It is essential that we understand the causes of this use-induced degradation of our auditory abilities, so that we might find ways to overcome it. The hair cells of the inner ear allow us to sense the mechanical vibrations of sound by amplifying and oscillating with incoming frequencies of sound. Both these processes of amplification and oscillation can be quite harmful to hair cells if done improperly, and thus present studies will address how hair cells may overcome these potential causes of use-induced degradation. ? ? ? ?
| LeBoeuf, Adria C; Ó Maoiléidigh, D; Hudspeth, A J (2011) Divalent counterions tether membrane-bound carbohydrates to promote the cohesion of auditory hair bundles. Biophys J 101:1316-25 |
