Since Georg von Bekesy laid out the place theory of the hearing, researchers have been working to understand the remarkable tuning properties of mammalian hearing. Because access to the cochlea is restricted in live animals, and important aspects of hearing are destroyed in dead ones, models play a key role in interpreting local measurements. Over the years our lab has progressively added more anatomical and physiological details to the modeling, always with the intent of interpreting experimental results. Examples are how cochlear coiling affects low frequency hearing, how the tectorial membrane introduces a second traveling wave that activates the outer hair cells and helps to excite inner hair cells, and how mechanical properties of tissues from the inner ear are important factors to be considered in development, repair, and normal function. Mechanical properties can be measured by the atomic force microscope (AFM) in our lab. These properties can reflect cytoskeletal changes as a result of altered protein expression in the cells of the inner ear that have been be altered by genetic manipulations. Thus our lab provides and important link between molecular genetics, cochlear development, and the physiology of hearing. Collaborations with the Manoussaki and Waterman labs involve of the use of the AFM to measure cell and substrate stiffness to assess how these factors influence cell motility, which has important implications for understanding development, pathophysiology, and the repair of tissues. In cochlear mechanics we have made progress this year in elucidating the importance of the phase of the tectorial membrane relative to the vibration of the basilar membrane on the activation of the cochlear amplifier, and the importance of these phases in inducing stimulated acoustic emissions. This year in cell mechanics we have developed new methods to measure membrane tension,intracellular pressure, and membrane cortex elastic and bending moduli in cells using the AFM. We have also made progress in elucidating factors affecting migration of confined melanoma cells.

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20
Fiscal Year
2015
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Name
Deafness & 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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