The electromechanical processes responsible for fine-tuning in the cochlea are still a matter of controversy. Using our recently developed mathematical model, it was shown that when motility and force generation of independently acting outer hair cells are assumed to be the source of activity, the low-pass filter property of isolated hair cells clearly limits the degree to which waveforms on the cochlear partition can be sharpened. This multi-degree of freedom model was used to determine the space-frequency characteristics of the putative cochlear amplifier that enables the model to reproduce experimentally- determined tuning characteristics, assuming only that outer hair cells are activated by the motion of the tectorial membrane and exert forces on both the reticular lamina and basilar membrane. It was found that outer hair cells must not only sense localized motions, but must also act synergistically to sense the local wavelength along the cochlear partition. This model of cochlear mechanics has been extended to include nonlinear effects induced by saturation of the cochlear amplifier. We are now able to compute compression of the cochlear input/output relation (basilar membrane velocity vs. input pressure at the stapes) and harmonic distortion of basilar membrane time waveforms along the cochlear partition for a pure tone input. It is anticipated that this new theory will be able to also increase understanding on a variety on nonlinear phenomena including the production of combination tones, two-tone suppression, and oto-acoustic emissions. We have extended the model to include coiling of the cochlear partition. Our theory predicts that coiling geometrically amplifies low frequency waves up to 20 dB compared to a straight cochlea having otherwise identical properties. We found the low-frequency hearing limit of mammals strongly depends on the coiling. Signifcant progress has been made in determining the radial structure of the traveling wave. We are developing computer codes to analyze fluid-solid interaction and motion in the organ of Corti and we are beginning to compare results with data obtained from the hemicochlea preparation. We find significant radial motion of the tectorial membrane(TM). We have begun experiments using the atomic force microscope to measure material properties of tissues isolated from the organ of Corti. We have the first map of elasticity of the mammalian tectorial membrane. We found that the tectorial membrane softens in the vicinity of outer hair cell insertions. We have just measured the anisotropic elastic moduli of the TM, and are currently developing methods to measure mechanical properties at acoustic frequencies using the AFM.

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National Institute on Deafness and Other Communication Disorders
United States
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Gavara, Núria; Chadwick, Richard S (2016) Relationship between cell stiffness and stress fiber amount, assessed by simultaneous atomic force microscopy and live-cell fluorescence imaging. Biomech Model Mechanobiol 15:511-23
Drummond, Meghan C; Barzik, Melanie; Bird, Jonathan E et al. (2015) Live-cell imaging of actin dynamics reveals mechanisms of stereocilia length regulation in the inner ear. Nat Commun 6:6873
Chadwick, Richard S; Lamb, Jessica S; Manoussaki, Daphne (2014) Stimulated acoustic emissions from coupled strings. J Eng Math 84:147-153
Szarama, Katherine B; Gavara, Núria; Petralia, Ronald S et al. (2012) Cytoskeletal changes in actin and microtubules underlie the developing surface mechanical properties of sensory and supporting cells in the mouse cochlea. Development 139:2187-97
Zhang, Duan-Sun; Piazza, Valeria; Perrin, Benjamin J et al. (2012) Multi-isotope imaging mass spectrometry reveals slow protein turnover in hair-cell stereocilia. Nature 481:520-4
Lamb, Jessica S; Chadwick, Richard S (2011) Dual traveling waves in an inner ear model with two degrees of freedom. Phys Rev Lett 107:088101
Smith, Sonya T; Chadwick, Richard S (2011) Simulation of the response of the inner hair cell stereocilia bundle to an acoustical stimulus. PLoS One 6:e18161
Gavara, Núria; Manoussaki, Daphne; Chadwick, Richard S (2011) Auditory mechanics of the tectorial membrane and the cochlear spiral. Curr Opin Otolaryngol Head Neck Surg 19:382-7
Gavara, Núria; Chadwick, Richard S (2009) Collagen-based mechanical anisotropy of the tectorial membrane: implications for inter-row coupling of outer hair cell bundles. PLoS One 4:e4877
Chadwick, Richard S; Liao, Zhijie (2008) High-Frequency Oscillations of a Sphere in a Viscous Fluid near a Rigid Plane. SIAM Rev Soc Ind Appl Math 50:313-322

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