The long-term goal of the proposed research is to understand the inner ear mechanisms that determine the neural code that relates sounds to the neural messages sent to the brain. Knowledge of these mechanisms is important for several reasons: (1) It is an intrinsically interesting scientific problem involving integrated knowledge of mechanical, electrical, biological, and chemical processes at the organ, cellular, membrane, and molecular levels. (2) The results should have significance for sensory reception in general, for mechanoreception in particular, and especially for understanding the acoustico-lateralis systems which include the lateral-line organs found in fish and amphibia as well as vestibular and auditory organs found in all vertebrates. (3) 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, speech communication systems, and speech-recognition systems. The specific objectives focus on understanding micromechanical processes by which sound-induced motions of the receptor organ stimulate motions of hair bundles. The tectorial membrane overlies the mechanically sensitive hair bundles and must therefore play a key role in mechanical stimulation of hair cells. However, little is known about even the most basic material properties of the tectorial membrane. Theoretical and experimental studies of the material properties of the tectorial membrane are proposed, in which direct measurements are compared to models, which relate material properties to the molecular architecture of the tectorial membrane and in vitro experimental measurements of sound-induced motions of hair bundles and the overlying tectorial membrane are proposed to directly characterize the role of the tectorial membrane in hearing.
| 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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