Meeting Abstract
S1.9 Sunday, Jan. 4 Macro- and micro-mechanics of hair-cell transduction COREY, David P*; KARAVITAKI, Domenica; SOTOMAYOR, Marcos; Harvard Medical School; Harvard Medical School; Harvard Medical School dcorey@hms.harvard.edu
The transduction channels of hair cells are located at the tips of the stereocilia that extend as a bundle from the top of each cell. A positive deflection of the bundle increases tension on tip links that extend between adjacent stereocilia; tip links convey tension to transduction channels to open them. To understand how tension opens channels, we must understand how tension depends on deflection. When the tallest stereocilia are moved, the bundle moves as a unit, indicating the presence of a strong cohesive force between adjacent stereocilia that nevertheless permits stereocilia to shear past one another. If the tip links provide cohesion, then the transduction channels in a column of stereocilia are mechanically in series with one another. If an independent mechanism exists for a sort of sliding adhesion between stereocilia, then the channels are mechanically in parallel. We have found with high resolution strobe illumination that, even in the absence of tip links and most other links, stereocilia adhere tightly to each other and separate by <10 nm even for very large deflections. Channels are thus in parallel and independent. Theories of transduction, confirmed by micromechanical measurements, propose an elastic gating spring in series with the channels. Although tip links were initially thought to be this spring, their morphology in EM and their invariant length argued that they are not extensible. Tip links are most likely composed of a parallel dimer of cadherin 23 in series with a dimer of protocadherin 15. We have used steered molecular dynamics to model the elasticity of tip-link cadherins, and find that they are unlikely to be the gating spring. In addition, we find that cadherin mutations that cause deafness in humans are likely to reduce the breaking strength of the tip link.
