Auditory detection starts with the deflection of the hair bundle, a mechano-sensory organelle that projects from the apical surface of epithelial “hair cell” in the inner ear (Fig. 1).
Mechanosensitivity stems from the direct mechanical activation of ion channels by tension changes in oblique tip links that interconnect neighbouring stereocilia within the hair bundle.
Our experiments demonstrate that the hair bundle behaves not only as a mechanosensory but also as a sort of oscillatory micro-muscle that can actively amplify the hair cell’s responsiveness to sinusoidal stimuli (Martin et Hudspeth, 1999). Elastic coupling between cells enhances the sensitivity and the frequency selectivity of auditory detection (Barral et al, 2010), so that the sensory unit of the inner ear is composed of a few tens of hair cells. The hair-bundle amplifier offers double benefit for hearing: it enlarges the range of sound intensities that can be heard by amplifying only the weakest sounds and sharpens frequency selectivity by filtering the input to the hair cell. Interestingly, the ear does not work as a high-fidelity sound receiver, introducing “phantom tones” that are not present in the acoustic input. We showed at the single-cell level that the hair-bundle amplifier produces distortions with properties that are characteristic of the phantom tones that are perceived in human hearing (Barral and Martin, 2012). To interpret quantitatively our observations, we have built a theoretical description of active hair-bundle motility that is based on a dynamic interplay between mechanosensitive ion channels, molecular motors and electro-mechanical feedback by calcium ions (Tinevez et al., 2007; Bormuth et al., 2014). Gating of the transduction channels produces internal forces that effectively reduce hair-bundle stiffness and increase hair-bundle friction (Bormuth et al., 2014). Gating forces can be so large as to result in negative bundle stiffness, a mechanical instability that foster motor-driven oscillation of the hair-cell bundle and in turn mechanical amplification.
In a complementary bio-mimetic approach to the hair-bundle oscillator (Fig. 2), we have also shown in vitro, with a minimal set of purified proteins, that autonomous mechanical oscillations can emerge from the collective properties of molecular motors (Plaçais et al, 2009). We are currently developing experiments to identify and control the biophysical parameters that determine the active biomechanical behaviour of the system.
Our results promote a general principle of sound detection that is based on nonlinear amplification by self-sustained “critical” oscillators in the inner ear (Hudspeth et al, 2010). An active oscillator is ideally suited for hearing, but only for detection near its characteristic frequency of oscillation. Processing complex sounds such as those relevant to speech or music calls for the operation of a set of oscillators in the cochlea with characteristic frequencies that span the auditory range. Determining the mechanisms that tune the frequency of active oscillation over a broad range (20 Hz to 20 kHz for human hearing) remains a major challenge for ongoing and future experiments. In the long term, we hope that this research may serve as a guiding framework to design novel devices for patients suffering from severe sensorineural hearing loss.