Based on its strategic location, the tectorial membrane (TM) has long been believed to play an essential role in hearing, but the cochlear mechanisms remain unclear. We propose research to improve our understanding of the functional role of the TM in determining (1) the remarkable properties of normal hearing - including its exquisite sensitivity and frequency selectivity - as well as (2) the hearing loss associated with genetic mutations of the TM and other cochlear pathologies. The proposed research is organized in three related aims.
Aim 1 : We propose to measure dynamic properties of the TM to determine the molecular origin of physiologically important properties such as shearing stiffness and loss moduli, charge density and associated electrokinetic behaviors, and traveling waves of the TM.
Aim 2 : We propose to measure the effects of genetic manipulations on TM dynamic properties. Measurement of TM waves, longitudinal coupling, charge density and electrokinetics of TMs in genetically modified mice will provide a framework for understanding the physical basis of the corresponding hearing disorders.
Aim 3 : We propose to measure interactions of the TM with other cochlear structures in an isolated, intact cochlea. We will measure relative motions of the TM and hair bundles in response to stapes motion. These measurements will provide direct tests of the TM's role in stimulating the hair bundles and spreading excitation along the cochlear spiral. Results from these three aims will increase our understanding of the cochlear mechanisms that underlie both normal and abnormal hearing. This knowledge has important practical applications for the delineation of inner-ear disorders (and concomitant suggestions for treatment) and for the design of speech-processing devices such as cochlear implants, hearing aids, and speech-recognition systems.
Our ability to communicate with each other and to navigate through acoustically rich environments depends on the detection and analysis of sounds by the inner ear. Genetic studies have shown that the tectorial membrane plays a key role in this analysis, but little is known about the underlying mechanisms. The proposed research to clarify these mechanisms will improve our understanding of both normal and impaired hearing and will be important for the design of speech-processing devices such as cochlear implants, hearing aids, and speech-communication and speech-recognition systems.
|Wadhwa, Neal; Chen, Justin G; Sellon, Jonathan B et al. (2017) Motion microscopy for visualizing and quantifying small motions. Proc Natl Acad Sci U S A 114:11639-11644|
|Sellon, Jonathan B; Ghaffari, Roozbeh; Freeman, Dennis M (2017) Geometric Requirements for Tectorial Membrane Traveling Waves in the Presence of Cochlear Loads. Biophys J 112:1059-1062|
|Farrahi, Shirin; Ghaffari, Roozbeh; Sellon, Jonathan B et al. (2016) Tectorial Membrane Traveling Waves Underlie Sharp Auditory Tuning in Humans. Biophys J 111:921-4|
|Sellon, Jonathan B; Farrahi, Shirin; Ghaffari, Roozbeh et al. (2015) Longitudinal spread of mechanical excitation through tectorial membrane traveling waves. Proc Natl Acad Sci U S A 112:12968-73|
|Sellon, Jonathan B; Ghaffari, Roozbeh; Farrahi, Shirin et al. (2014) Porosity controls spread of excitation in tectorial membrane traveling waves. Biophys J 106:1406-13|
|Ghaffari, Roozbeh; Page, Scott L; Farrahi, Shirin et al. (2013) Electrokinetic properties of the mammalian tectorial membrane. Proc Natl Acad Sci U S A 110:4279-84|
|Masaki, Kinuko; Ghaffari, Roozbeh; Gu, Jianwen Wendy et al. (2010) Tectorial membrane material properties in Tecta(Y)(1870C/+) heterozygous mice. Biophys J 99:3274-81|
|Ghaffari, Roozbeh; Aranyosi, Alexander J; Richardson, Guy P et al. (2010) Tectorial membrane travelling waves underlie abnormal hearing in Tectb mutant mice. Nat Commun 1:96|
|Masaki, Kinuko; Gu, Jianwen Wendy; Ghaffari, Roozbeh et al. (2009) Col11a2 deletion reveals the molecular basis for tectorial membrane mechanical anisotropy. Biophys J 96:4717-24|
|Gu, Jianwen Wendy; Hemmert, Werner; Freeman, Dennis M et al. (2008) Frequency-dependent shear impedance of the tectorial membrane. Biophys J 95:2529-38|
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