It is increasingly clear that the extraordinary acoustical sensitivity and frequency selectivity that are hallmarks of our sense of hearing arise from micromechanical mechanisms. Genetic manipulations have shown that the tectorial membrane (TM) plays an essential role in this process. But that role remains enigmatic, in large part because of the paucity of direct measurements of TM properties. We propose research to improve our understanding of the role of the TM with studies in three related categories, [a.] We propose to measure material properties of the TM to determine their molecular basis and functional significance. We will combine mechanical, chemical, osmotic and electrical measurements of the TM to characterize its material properties as a function of longitudinal position in the cochlea. These material properties will provide a quantitative basis for understanding the functional role of the TM in normal hearing, [b.] We propose to measure effects of genetic mutations on material properties of the TM. Several human genetic disorders of hearing result from mutations of TM proteins. Measurements of the material properties of TMs from mouse models of these disorders will provide a better understanding of the physical basis of the human disorders of hearing, and will elucidate the molecular basis of the material properties of the TM. [c.] We propose to measure coupling of the TM to other cochlear structures in an isolated, but intact cochlea. We will apply displacements to the stapes and measure the resulting motions of the TM and hair bundles of inner and outer hair cells. These measurements will provide direct tests of hypotheses about the role of the TM in cochlear mechanics. The practical benefits of this knowledge should include more precise delineation of inner ear disorders, suggestions for treatment, development of prosthetic devices, and>incorporation of knowledge of inner-ear processing into the design of systems for processing speech.... :??

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000238-25
Application #
7738935
Study Section
Auditory System Study Section (AUD)
Program Officer
Donahue, Amy
Project Start
1984-06-01
Project End
2011-11-30
Budget Start
2009-12-01
Budget End
2010-11-30
Support Year
25
Fiscal Year
2010
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Internal Medicine/Medicine
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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
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
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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