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 we found that there is strong coupling of OHC bundles at a given longitudinal location. We have developed methods to measure mechanical properties at acoustic frequencies using frequency modulation AFM. We are currently developing methods to study force transmission on the reticular lamina, and models for otoacustic emissions.

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National Institute on Deafness and Other Communication Disorders
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Logue, Jeremy S; Cartagena-Rivera, Alexander X; Chadwick, Richard S (2018) c-Src activity is differentially required by cancer cell motility modes. Oncogene 37:2104-2121
Van Itallie, Christina M; Tietgens, Amber Jean; Aponte, Angel et al. (2018) MARCKS-related protein regulates cytoskeletal organization at cell-cell and cell-substrate contacts in epithelial cells. J Cell Sci 131:
Cartagena-Rivera, Alexander X; Van Itallie, Christina M; Anderson, James M et al. (2017) Apical surface supracellular mechanical properties in polarized epithelium using noninvasive acoustic force spectroscopy. Nat Commun 8:1030
Gavara, NĂºria; 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
Chadwick, Richard S (2016) A Dual Probe and Two Tones Reveal Dual Waves in the Cochlea. Biophys J 111:1587-1588
Cartagena-Rivera, Alexander X; Logue, Jeremy S; Waterman, Clare M et al. (2016) Actomyosin Cortical Mechanical Properties in Nonadherent Cells Determined by Atomic Force Microscopy. Biophys J 110:2528-39
Logue, Jeremy S; Cartagena-Rivera, Alexander X; Baird, Michelle A et al. (2015) Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration. Elife 4:
Manoussaki, Daphne; Shin, William D; Waterman, Clare M et al. (2015) Cytosolic pressure provides a propulsive force comparable to actin polymerization during lamellipod protrusion. Sci Rep 5:12314
Chadwick, Richard S; Lamb, Jessica S; Manoussaki, Daphne (2014) Stimulated acoustic emissions from coupled strings. J Eng Math 84:147-153
Lamb, Jessica S; Chadwick, Richard S (2014) Phase of shear vibrations within cochlear partition leads to activation of the cochlear amplifier. PLoS One 9:e85969

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