Outer hair cells (OHC) are required for normal mammalian hearing. They convert electrical to mechanical energy and contribute to the cochlear amplifier that magnifies and refines sound vibrations in the inner ear. Interfering with their electromechanical force generating mechanism results in hearing loss. The mechanism responsible for this force production resides in the OHC's plasma membrane. All membranes appear able to convert electrical into mechanical force. The OHC membrane contains a protein called prestin thatenhances the process. In addition, the cylindrical OHCs are effective at taking the membrane generated force and directing it parallel to their longitudinal axis. This is achieved by an elegant, three layered, composite nanostructure that is as biologically unique as the role it plays in hearing. One goal of this proposal is to understand how prestin and the nanoscale mechanical anatomy of the lateral wall facilitate OHC electromechanical force production, particularly at acoustic frequencies. The role of prestin is determined by examining how its presence or absence alters electromechanical transduction. The effect of drugs and changes in the intracellular chloride concentration known to alter electromechanical transduction in the OHC and thereby modulate hearing are assessed for all experimental manipulations. Coordinated experimental, mathematical and computational approaches will determine how the organization of the lateral wall directs the electromechanical force generated by the plasma membrane.
Three specific aims i nvestigate OHC mechanical properties and electromechancial transduction at progressively larger scales beginning with the cell membrane and ending with the whole cell. Voltage-clamp and optical tweezers are used together in all three specific aims.
Specific Aim 1 examines electromechanical transduction in the plasma membrane by investigating the mechanical response of membrane tethers to changes in the transmembrane potential. These experiments will determine the electromechanical transduction coefficient for the membrane alone.
Specific Aim 2 probes the response of the lateral wall and Specific Aim 3 examines the mechanics and electromechanics of the whole cell. The final result will be a complete description of OHC electromechanical force production and its role in hearing.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Auditory System Study Section (AUD)
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Freeman, Nancy
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Baylor College of Medicine
Schools of Medicine
United States
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Brownell, William E (2017) What Is Electromotility? -The History of Its Discovery and Its Relevance to Acoustics. Acoust Today 13:20-27
Sarshar, Mohammad; Lu, Thompson; Anvari, Bahman (2016) Combined optical micromanipulation and interferometric topography (COMMIT). Biomed Opt Express 7:1365-74
Araya, Mussie; Brownell, William E (2016) Nanotechnology in Auditory Research: Membrane Electromechanics in Hearing. Methods Mol Biol 1427:349-62
Yamashita, Tetsuji; Hakizimana, Pierre; Wu, Siva et al. (2015) Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. PLoS Genet 11:e1005500
Powers, Richard J; Kulason, Sue; Atilgan, Erdinc et al. (2014) The local forces acting on the mechanotransduction channel in hair cell stereocilia. Biophys J 106:2519-28
Sarshar, Mohammad; Wong, Winson T; Anvari, Bahman (2014) Comparative study of methods to calibrate the stiffness of a single-beam gradient-force optical tweezers over various laser trapping powers. J Biomed Opt 19:115001
Farrell, Brenda; Qian, Feng; Kolomeisky, Anatoly et al. (2013) Measuring forces at the leading edge: a force assay for cell motility. Integr Biol (Camb) 5:204-14
Khatibzadeh, Nima; Spector, Alexander A; Brownell, William E et al. (2013) Effects of plasma membrane cholesterol level and cytoskeleton F-actin on cell protrusion mechanics. PLoS One 8:e57147
Hakizimana, Pierre; Brownell, William E; Jacob, Stefan et al. (2012) Sound-induced length changes in outer hair cell stereocilia. Nat Commun 3:1094
Roy, Sitikantha; Brownell, William E; Spector, Alexander A (2012) Modeling electrically active viscoelastic membranes. PLoS One 7:e37667

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