Machanical Frequency Tuning by the Hair Bundle of Mechanosensory Hair Cells

Hearing starts with the deflection of the hair bundle, a cohesive tuft of actin-based cylindrical protrusions—the stereocilia—that gives their name to the mechanosensory hair cells of the inner ear. Tension changes in tip links interconnecting the stereocilia modulate the open probability of ion channels located at the stereociliary tips, resulting in an electrical response. Hair cells are tuned to a characteristic frequency of the stimulus and spatially distributed in auditory organs according to a tonotopic map. Here we review micromechanical measurements on single hair bundles implicating this mechanosensory antenna in mechanical frequency tuning of the hair cell. In the frog saccule, a dynamic interplay between negative stiffness mediated by ion channels’ gating forces and delayed force feedback owing to both myosin motors pulling on the tip links and channel reclosure by calcium ions brings the hair bundle to the vicinity of an oscillatory instability—a Hopf bifurcation. Driven by this active process, the hair bundle works as a resonant system that provides nonlinear amplification of faint signals near its frequency of spontaneous oscillation. In addition, in the rat cochlea, we found that tonotopy is associated with gradients of stiffness and resting mechanical tension, both at the cellular scale of a whole hair bundle and at the molecular scale of a single tip link. Finally, in the frog saccule, recent observations revealed a strong coupling between actin polymerization in the hair bundle, which determines the bundle size and stiffness, and mechanoelectrical transduction, possibly via a formin-dependent pathway that controls the number and length of actin filaments in stereocilia. These findings provide an entry point to the mechanism that maintains the morphology of the hair bundle according to the bundle's function as a frequency-selective antenna.