Mécano-sensibilité active des cellules ciliées de l’oreille interne

Publications de l’équipe

Année de publication : 2018

Jérémie Barral, Frank Jülicher, Pascal Martin (2018 Feb 6)

Friction from Transduction Channels’ Gating Affects Spontaneous Hair-Bundle Oscillations.

Biophysical journal : 425-436 : DOI : S0006-3495(17)31251-1 En savoir plus
Résumé

Hair cells of the inner ear can power spontaneous oscillations of their mechanosensory hair bundle, resulting in amplification of weak inputs near the characteristic frequency of oscillation. Recently, dynamic force measurements have revealed that delayed gating of the mechanosensitive ion channels responsible for mechanoelectrical transduction produces a friction force on the hair bundle. The significance of this intrinsic source of dissipation for the dynamical process underlying active hair-bundle motility has remained elusive. The aim of this work is to determine the role of friction in spontaneous hair-bundle oscillations. To this end, we characterized key oscillation properties over a large ensemble of individual hair cells and measured how viscosity of the endolymph that bathes the hair bundles affects these properties. We found that hair-bundle movements were too slow to be impeded by viscous drag only. Moreover, the oscillation frequency was only marginally affected by increasing endolymph viscosity by up to 30-fold. Stochastic simulations could capture the observed behaviors by adding a contribution to friction that was 3-8-fold larger than viscous drag. The extra friction could be attributed to delayed changes in tip-link tension as the result of the finite activation kinetics of the transduction channels. We exploited our analysis of hair-bundle dynamics to infer the channel activation time, which was ∼1 ms. This timescale was two orders-of-magnitude shorter than the oscillation period. However, because the channel activation time was significantly longer than the timescale of mechanical relaxation of the hair bundle, channel kinetics affected hair-bundle dynamics. Our results suggest that friction from channel gating affects the waveform of oscillation and that the channel activation time can tune the characteristic frequency of the hair cell. We conclude that the kinetics of transduction channels’ gating plays a fundamental role in the dynamic process that shapes spontaneous hair-bundle oscillations.

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Année de publication : 2014

Pascal Martin (2014 Aug 21)

All that jazz coming out of my ears.

Biophysical journal : 800-2 : DOI : 10.1016/j.bpj.2014.07.011 En savoir plus
Résumé

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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 En savoir plus
Résumé

Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. Friction is generally thought to result mainly from viscous drag by the surrounding fluid. We demonstrate here that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle. We characterized friction by analyzing hysteresis in the force-displacement relation of single hair-cell bundles in response to periodic triangular stimuli. For bundle velocities high enough to outrun adaptation, we found that frictional forces were maximal within the narrow region of deflections that elicited significant channel gating, plummeted upon application of a channel blocker, and displayed a sublinear growth for increasing bundle velocity. At low velocity, the slope of the relation between the frictional force and velocity was nearly fivefold larger than the hydrodynamic friction coefficient that was measured when the transduction machinery was decoupled from bundle motion by severing tip links. A theoretical analysis reveals that channel friction arises from coupling the dynamics of the conformational change associated with channel gating to tip-link tension. Varying channel properties affects friction, with faster channels producing smaller friction. We propose that this intrinsic source of friction may contribute to the process that sets the hair cell’s characteristic frequency of responsiveness.

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Année de publication : 2012

L Dinis, P Martin, J Barral, J Prost, J F Joanny (2012 Dec 11)

Fluctuation-response theorem for the active noisy oscillator of the hair-cell bundle.

Physical review letters : 160602 En savoir plus
Résumé

The hair bundle of sensory cells in the vertebrate ear provides an example of a noisy oscillator close to a Hopf bifurcation. The analysis of the data from both spontaneous and forced oscillations shows a strong violation of the fluctuation-dissipation theorem, revealing the presence of an underlying active process that keeps the system out of equilibrium. Nevertheless, we show that a generalized fluctuation-dissipation theorem, valid for nonequilibrium steady states, is fulfilled within the limits of our experimental accuracy and computational approximations, when the adequate conjugate degrees of freedom are chosen.

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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 En savoir plus
Résumé

Processing of two-tone stimuli by the auditory system introduces prominent masking of one frequency component by the other as well as additional « phantom » tones that are absent in the sound input. Mechanical correlates of these psychophysical phenomena have been observed in sound-evoked mechanical vibrations of the mammalian cochlea and are thought to originate in sensory hair cells from the intrinsic nonlinearity associated with mechano-electrical transduction by ion channels. However, nonlinearity of the transducer is not sufficient to explain the rich phenomenology of two-tone interferences in hearing. Here we show that active oscillatory movements of single hair-cell bundles elicit two-tone suppression and distortions that are shaped by nonlinear amplification of periodic stimuli near the characteristic frequency of spontaneous oscillations. When both stimulus frequencies enter the bandwidth of the hair-bundle amplifier, two-tone interferences display level functions that are characteristic both of human psychoacoustics and of in vivo mechanical measurements in auditory organs. Our work distinguishes the frequency-dependent nonlinearity that emerges from the active process that drives the hair bundle into spontaneous oscillations from the passive nonlinear compliance associated with the direct gating of transduction channels by mechanical force. Numerical simulations based on a generic description of an active dynamical system poised near an oscillatory instability–a Hopf bifurcation–account quantitatively for our experimental observations. In return, we conclude that the properties of two-tone interferences in hearing betray the workings of self-sustained « critical » oscillators, which function as nonlinear amplifying elements in the inner ear.

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Année de publication : 2011

Jérémie Barral, Pascal Martin (2011 Aug 10)

The physical basis of active mechanosensitivity by the hair-cell bundle.

Current opinion in otolaryngology & head and neck surgery : 369-75 : DOI : 10.1097/MOO.0b013e32834a8c33 En savoir plus
Résumé

Hearing starts with the deflection of the hair bundle that sits on top of each mechanosensory hair cell. Recent advances indicate that the hair bundle mechanically amplifies its inputs to participate in the active process that boosts the ear’s technical specifications. This review integrates experimental and modeling studies to dissect the mechanisms of active mechanosensation by the hair-cell bundle.

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Année de publication : 2010

J Ashmore, P Avan, W E Brownell, P Dallos, K Dierkes, R Fettiplace, K Grosh, C M Hackney, A J Hudspeth, F Jülicher, B Lindner, P Martin, J Meaud, C Petit, J Santos-Sacchi, J R Santos Sacchi, B Canlon (2010 Jun 15)

The remarkable cochlear amplifier.

Hearing research : 1-17 : DOI : 10.1016/j.heares.2010.05.001 En savoir plus
Résumé

This composite article is intended to give the experts in the field of cochlear mechanics an opportunity to voice their personal opinion on the one mechanism they believe dominates cochlear amplification in mammals. A collection of these ideas are presented here for the auditory community and others interested in the cochlear amplifier. Each expert has given their own personal view on the topic and at the end of their commentary they have suggested several experiments that would be required for the decisive mechanism underlying the cochlear amplifier. These experiments are presently lacking but if successfully performed would have an enormous impact on our understanding of the cochlear amplifier.

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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 En savoir plus
Résumé

The sense of hearing achieves its striking sensitivity, frequency selectivity, and dynamic range through an active process mediated by the inner ear’s mechanoreceptive hair cells. Although the active process renders hearing highly nonlinear and produces a wealth of complex behaviors, these various characteristics may be understood as consequences of a simple phenomenon: the Hopf bifurcation. Any critical oscillator operating near this dynamic instability manifests the properties demonstrated for hearing: amplification with a specific form of compressive nonlinearity and frequency tuning whose sharpness depends on the degree of amplification. Critical oscillation also explains spontaneous otoacoustic emissions as well as the spectrum and level dependence of the ear’s distortion products. Although this has not been realized, several valuable theories of cochlear function have achieved their success by incorporating critical oscillators.

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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 En savoir plus
Résumé

The vertebrate ear benefits from nonlinear mechanical amplification to operate over a vast range of sound intensities. The amplificatory process is thought to emerge from active force production by sensory hair cells. The mechano-sensory hair bundle that protrudes from the apical surface of each hair cell can oscillate spontaneously and function as a frequency-selective, nonlinear amplifier. Intrinsic fluctuations, however, jostle the response of a single hair bundle to weak stimuli and seriously limit amplification. Most hair bundles are mechanically coupled by overlying gelatinous structures. Here, we assayed the effects of mechanical coupling on the hair-bundle amplifier by combining dynamic force clamp of a hair bundle from the bullfrog’s saccule with real-time stochastic simulations of hair-bundle mechanics. This setup couples the hair bundle to two virtual hair bundles, called cyber clones, and mimics a situation in which the hair bundle is elastically linked to two neighbors with similar characteristics. We found that coupling increased the coherence of spontaneous hair-bundle oscillations. By effectively reducing noise, the synergic interplay between the hair bundle and its cyber clones also enhanced amplification of sinusoidal stimuli. All observed effects of coupling were in quantitative agreement with simulations. We argue that the auditory amplifier relies on hair-bundle cooperation to overcome intrinsic noise limitations and achieve high sensitivity and sharp frequency selectivity.

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Thomas Guérin, Jacques Prost, Pascal Martin, Jean-François Joanny (2010 Jan 16)

Coordination and collective properties of molecular motors: theory.

Current opinion in cell biology : 14-20 : DOI : 10.1016/j.ceb.2009.12.012 En savoir plus
Résumé

Many cellular processes require molecular motors to produce motion and forces. Single molecule experiments have led to a precise description of how a motor works. Under most physiological conditions, however, molecular motors operate in groups. Interactions between motors yield collective behaviors that cannot be explained only from single molecule properties. The aim of this paper is to review the various theoretical descriptions that explain the emergence of collective effects in molecular motor assemblies. These include bidirectional motion, hysteretic behavior, spontaneous oscillations, and self-organization into dynamical structures. We discuss motors acting on the cytoskeleton both in a prescribed geometry such as in muscles or flagella and in the cytoplasm.

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Année de publication : 2009

Nicolas Michalski, Vincent Michel, Elisa Caberlotto, Gaelle M Lefèvre, Alexander F J van Aken, Jean-Yves Tinevez, Emilie Bizard, Christophe Houbron, Dominique Weil, Jean-Pierre Hardelin, Guy P Richardson, Corné J Kros, Pascal Martin, Christine Petit (2009 Sep 17)

Harmonin-b, an actin-binding scaffold protein, is involved in the adaptation of mechanoelectrical transduction by sensory hair cells.

Pflügers Archiv : European journal of physiology : 115-30 : DOI : 10.1007/s00424-009-0711-x En savoir plus
Résumé

We assessed the involvement of harmonin-b, a submembranous protein containing PDZ domains, in the mechanoelectrical transduction machinery of inner ear hair cells. Harmonin-b is located in the region of the upper insertion point of the tip link that joins adjacent stereocilia from different rows and that is believed to gate transducer channel(s) located in the region of the tip link’s lower insertion point. In Ush1c (dfcr-2J/dfcr-2J) mutant mice defective for harmonin-b, step deflections of the hair bundle evoked transduction currents with altered speed and extent of adaptation. In utricular hair cells, hair bundle morphology and maximal transduction currents were similar to those observed in wild-type mice, but adaptation was faster and more complete. Cochlear outer hair cells displayed reduced maximal transduction currents, which may be the consequence of moderate structural anomalies of their hair bundles. Their adaptation was slower and displayed a variable extent. The latter was positively correlated with the magnitude of the maximal transduction current, but the cells that showed the largest currents could be either hyperadaptive or hypoadaptive. To interpret our observations, we used a theoretical description of mechanoelectrical transduction based on the gating spring theory and a motor model of adaptation. Simulations could account for the characteristics of transduction currents in wild-type and mutant hair cells, both vestibular and cochlear. They led us to conclude that harmonin-b operates as an intracellular link that limits adaptation and engages adaptation motors, a dual role consistent with the scaffolding property of the protein and its binding to both actin filaments and the tip link component cadherin-23.

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F Jülicher, K Dierkes, B Lindner, J Prost, P Martin (2009 Aug 25)

Spontaneous movements and linear response of a noisy oscillator.

The European physical journal. E, Soft matter : 449-60 : DOI : 10.1140/epje/i2009-10487-5 En savoir plus
Résumé

A deterministic system that operates in the vicinity of a Hopf bifurcation can be described by a single equation of a complex variable, called the normal form. Proximity to the bifurcation ensures that on the stable side of the bifurcation (i.e. on the side where a stable fixed point exists), the linear-response function of the system is peaked at the frequency that is characteristic of the oscillatory instability. Fluctuations, which are present in many systems, conceal the Hopf bifurcation and lead to noisy oscillations. Spontaneous hair bundle oscillations by sensory hair cells from the vertebrate ear provide an instructive example of such noisy oscillations. By starting from a simplified description of hair bundle motility based on two degrees of freedom, we discuss the interplay of nonlinearity and noise in the supercritical Hopf normal form. Specifically, we show here that the linear-response function obeys the same functional form as for the noiseless system on the stable side of the bifurcation but with effective, renormalized parameters. Moreover, we demonstrate in specific cases how to relate analytically the parameters of the normal form with added noise to effective parameters. The latter parameters can be measured experimentally in the power spectrum of spontaneous activity and linear-response function to external stimuli. In other cases, numerical solutions were used to determine the effects of noise and nonlinearities on these effective parameters. Finally, we relate our results to experimentally observed spontaneous hair bundle oscillations and responses to periodic stimuli.

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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 En savoir plus
Résumé

Spontaneous mechanical oscillations occur in various types of biological systems where groups of motor molecules are elastically coupled to their environment. By using an optical trap to oppose the gliding motion of a single bead-tailed actin filament over a substrate densely coated with myosin motors, we mimicked this condition in vitro. We show that this minimal actomyosin system can oscillate spontaneously. Our finding accords quantitatively with a general theoretical framework where oscillatory instabilities emerge generically from the collective dynamics of molecular motors under load.

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Année de 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 En savoir plus
Résumé

The dazzling sensitivity and frequency selectivity of the vertebrate ear rely on mechanical amplification of the hair cells’ responsiveness to small stimuli. As revealed by spontaneous oscillations and forms of mechanical excitability in response to force steps, the hair bundle that adorns each hair cell is both a mechanosensory antenna and a force generator that might participate in the amplificatory process. To study the various incarnations of active hair-bundle motility, we combined Ca(2+) iontophoresis with mechanical stimulation of single hair bundles from the bullfrog’s sacculus. We identified three classes of active hair-bundle movements: a hair bundle could be quiescent but display nonmonotonic twitches in response to either excitatory or inhibitory force steps, or oscillate spontaneously. Extracellular Ca(2+) changes could affect the kinetics of motion and, when large enough, evoke transitions between the three classes of motility. We found that the Ca(2+)-dependent location of a bundle’s operating point within its force-displacement relation controlled the type of movement observed. In response to an iontophoretic pulse of Ca(2+) or of a Ca(2+) chelator, a hair bundle displayed a movement whose polarity could be reversed by applying a static bias to the bundle’s position at rest. Moreover, such polarity reversal was accompanied by a 10-fold change in the kinetics of the Ca(2+)-evoked hair-bundle movement. A unified theoretical description, in which mechanical activity stems solely from myosin-based adaptation, could account for the fast and slow manifestations of active hair-bundle motility observed in frog, as well as in auditory organs of the turtle and the rat.

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Année de publication : 2004

Björn Nadrowski, Pascal Martin, Frank Jülicher (2004 Aug 11)

Active hair-bundle motility harnesses noise to operate near an optimum of mechanosensitivity.

Proceedings of the National Academy of Sciences of the United States of America : 12195-200 En savoir plus
Résumé

The ear relies on nonlinear amplification to enhance its sensitivity and frequency selectivity to oscillatory mechanical stimuli. It has been suggested that this active process results from the operation of dynamical systems that operate in the vicinity of an oscillatory instability, a Hopf bifurcation. In the bullfrog’s sacculus, a hair cell can display spontaneous oscillations of its mechanosensory hair bundle. The behavior of an oscillatory hair bundle resembles that of a critical oscillator. We present here a theoretical description of the effects of intrinsic noise on active hair-bundle motility. An oscillatory instability can result from the interplay between a region of negative stiffness in the bundle’s force-displacement relation and the Ca(2+)-regulated activity of molecular motors. We calculate a state diagram that describes the possible dynamical states of the hair bundle in the absence of fluctuations. Taking into account thermal fluctuations, the stochastic nature of transduction channels’ gating, and of the forces generated by molecular motors, we discuss conditions that yield a response function and spontaneous noisy movements of the hair bundle in quantitative agreement with previously published experiments. We find that the magnitude of the fluctuations resulting from the active processes that mediate mechanical amplification remains just below that of thermal fluctuations. Fluctuations destroy the phase coherence of spontaneous oscillations and restrict the bundle’s sensitivity as well as frequency selectivity to small oscillatory stimuli. We show, however, that a hair bundle studied experimentally operates near an optimum of mechanosensitivity in our state diagram.

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