Active Mechano-Sensitivity by Hair Cells in the Inner Ear

Martin

Pascal Martin Chef d'équipe Tel:

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).

A : Vue en microscopie à contraste interférentiel d’une cellule ciliée extraite de l’oreille interne de la grenouille taureau (Rana catesbeiana). B : Vue en microscopie électronique d’une touffe ciliaire. (sources : A : AJ Hudspeth, the Rockefeller University, New York ; B : P Gillespie, OHSU, Portland)
Figure 1: A: View of a single hair cell extracted from the saccule of the bullfrog (Rana catesbeiana). B : A scanning electron micrograph of a hair bundle. About 60 cylindrical processes, the stereocilia, are arranged in rows of increasing height. (sources : A : AJ Hudspeth, the Rockefeller University, New York ; B : P Gillespie, OHSU, Portland).

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.

A : Déclenchement d’une oscillation spontanée par augmentation de la concentration en ion Ca2+. Au-delà d’une valeur seuil de la concentration en calcium, on observe une bifurcation (bifurcation de Hopf) vers un comportement oscillant. La fréquence de l’oscillation augmente avec le calcium. B : Relation force-déplacement d’une touffe ciliaire oscillante. La touffe ciliaire présente une « raideur négative » dans la zone centrale de la relation force-déplacement. Les positions correspondantes sont instables.
Figure 2: A: From quiescence to spontaneous oscillations with Ca2+ iontophoresis. When the Ca2+ concentration is raised above a threshold value, we observe a bifurcation (Hopf bifurcation) towards an oscillatory behavior whose frequency increases with Ca2+. B: Force-displacement relation of an oscillatory hair bundle. The hair bundle displays a region of “negative stiffness” in the central region of the curve. The hair bundle cannot rest stably at the corresponding positions.

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.

Key publications

Year of publication 2014

Volker Bormuth, Jérémie Barral, Jean-François Joanny, Frank Jülicher, Pascal Martin (2014 May 5)

Transduction channels’ gating can control friction on vibrating hair-cell bundles in the ear.

Proceedings of the National Academy of Sciences of the United States of America : 7185-90 : DOI : 10.1073/pnas.1402556111

Year of publication 2012

Jérémie Barral, Pascal Martin (2012 May 3)

Phantom tones and suppressive masking by active nonlinear oscillation of the hair-cell bundle.

Proceedings of the National Academy of Sciences of the United States of America : E1344-51 : DOI : 10.1073/pnas.1202426109

Year of publication 2010

A J Hudspeth, Frank Jülicher, Pascal Martin (2010 Jun 10)

A critique of the critical cochlea: Hopf–a bifurcation–is better than none.

Journal of neurophysiology : 1219-29 : DOI : 10.1152/jn.00437.2010
Jérémie Barral, Kai Dierkes, Benjamin Lindner, Frank Jülicher, Pascal Martin (2010 Apr 19)

Coupling a sensory hair-cell bundle to cyber clones enhances nonlinear amplification.

Proceedings of the National Academy of Sciences of the United States of America : 8079-84 : DOI : 10.1073/pnas.0913657107

Year of publication 2009

P-Y Plaçais, M Balland, T Guérin, J-F Joanny, P Martin (2009 Jun 23)

Spontaneous oscillations of a minimal actomyosin system under elastic loading.

Physical review letters : 158102

Year of publication 2007

Jean-Yves Tinevez, Frank Jülicher, Pascal Martin (2007 Aug 17)

Unifying the various incarnations of active hair-bundle motility by the vertebrate hair cell.

Biophysical journal : 4053-67
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