Biophysical mechanisms underlying hearing loss associated with a shortened tectorial membrane

John S. Oghalai, Anping Xia, Christopher C. Liu, Simon S. Gao, Brian E. Applegate, Sunil Puria, Itay Rousso, Charles Steele

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The tectorial membrane (TM) connects to the stereociliary bundles of outer hair cells (OHCs). Herein, we summarize key experimental data and modeling analyses that describe how biophysical alterations to these connections underlie hearing loss. The heterozygous C1509G mutation in alpha tectorin produces partial congenital hearing loss that progresses in humans. We engineered this mutation in mice, and histology revealed that the TM was shortened. DIC imaging of freshly-dissected cochlea as well as imaging with optical coherence tomography indicated that the TM is malformed and only stimulates the first row of OHCs. Noise exposure produced acute threshold shifts that fully recovered in Tecta+/+ mice although there was some OHC loss within all three rows at the cochlear base. In contrast, threshold shifts only partially recovered in TectaC1509G/+ mice. This was associated with OHC loss more apically and nearly entirely within the first row. Young's modulus of the TM, measured using atomic force microscopy, was substantially reduced at the middle and basal regions. Both the wild-type and heterozygous conditions were simulated in a computational model. This demonstrated that the normalized stress distribution levels between the TM and the tall cilia were significantly elevated in the middle region of the heterozygous cochlea. Another feature of the Tecta C1509G/+ mutation is higher prestin expression within all three rows of OHCs. This increased electricallyevoked movements of the reticular lamina and otoacoustic emissions. Furthermore, electrical stimulation was associated with an increased risk of OHC death as measured by vital dye staining. Together, these findings indicate that uncoupling of the TM from some OHCs not only leads to partial hearing loss, but also puts the OHCs that remain coupled at higher risk. Both the mechanics of the malformed TM and increased electromotility contribute to this higher risk profile.

Original languageEnglish (US)
Title of host publicationWhat Fire is in Mine Ears
Subtitle of host publicationProgress in Auditory Biomechanics - Proceedings of the 11th International Mechanics of Hearing Workshop
Pages116-121
Number of pages6
DOIs
StatePublished - Dec 12 2011
Event11th International Mechanics of Hearing Workshop - What Fire is in Mine Ears: Progress in Auditory Biomechanics - Williamstown, MA, United States
Duration: Jul 16 2011Jul 22 2011

Publication series

NameAIP Conference Proceedings
Volume1403
ISSN (Print)0094-243X
ISSN (Electronic)1551-7616

Other

Other11th International Mechanics of Hearing Workshop - What Fire is in Mine Ears: Progress in Auditory Biomechanics
CountryUnited States
CityWilliamstown, MA
Period7/16/117/22/11

Keywords

  • cochlea
  • deafness
  • electromotility
  • hair cell
  • hearing
  • hearing loss
  • transduction

ASJC Scopus subject areas

  • Physics and Astronomy(all)

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  • Cite this

    Oghalai, J. S., Xia, A., Liu, C. C., Gao, S. S., Applegate, B. E., Puria, S., Rousso, I., & Steele, C. (2011). Biophysical mechanisms underlying hearing loss associated with a shortened tectorial membrane. In What Fire is in Mine Ears: Progress in Auditory Biomechanics - Proceedings of the 11th International Mechanics of Hearing Workshop (pp. 116-121). (AIP Conference Proceedings; Vol. 1403). https://doi.org/10.1063/1.3658070