Bridging the gap between physics and biology of hearing: Timing and amplification.

In mammals, the exquisite sensitivity and frequency selectivity of sound analysis rests on properly timed cycle-by-cycle feedback that compensates for friction and tunes the mechanical resonances of the auditory sensory organ. This feedback must operate at the highest audible frequencies, more than 100 kHz in some species, a feat given that it relies upon voltage-driven conformation changes of a protein called prestin, which forms an array along the lateral membrane of outer hair cell endowing them with electromotility. In the first place, the voltage that actuates prestin results from mechanotransduction of sound-induced vibrations by a mechanosensitive protein complex hosted in hair cell microvilli called stereocilia, whose nanometric deflections must ensure ion channel activation within microseconds. Many molecular assemblies and configurations allowing mechanosensitive detection to be pushed to such physical scales in terms of displacement and time, a unique requirement of hearing among mechanosensory systems, are still under active investigations.