Age-related degradation of tectorial membrane dynamics with loss of CEACAM16

Studies of genetic disorders of sensorineural hearing loss have been instrumental in delineating mechanisms that underlie the remarkable sensitivity and selectivity that are hallmarks of mammalian hearing. For example, genetic modifications of TECTA and TECTB, which are principal proteins that compr...

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Main Authors: Mansour, Amer, Sellon, Jonathan B, Filizzola, Daniel, Ghaffari, Roozbeh, Cheatham, Mary Ann, Freeman, Dennis M
Other Authors: Massachusetts Institute of Technology. Research Laboratory of Electronics
Format: Article
Language:English
Published: Elsevier BV 2022
Online Access:https://hdl.handle.net/1721.1/143540
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author Mansour, Amer
Sellon, Jonathan B
Filizzola, Daniel
Ghaffari, Roozbeh
Cheatham, Mary Ann
Freeman, Dennis M
author2 Massachusetts Institute of Technology. Research Laboratory of Electronics
author_facet Massachusetts Institute of Technology. Research Laboratory of Electronics
Mansour, Amer
Sellon, Jonathan B
Filizzola, Daniel
Ghaffari, Roozbeh
Cheatham, Mary Ann
Freeman, Dennis M
author_sort Mansour, Amer
collection MIT
description Studies of genetic disorders of sensorineural hearing loss have been instrumental in delineating mechanisms that underlie the remarkable sensitivity and selectivity that are hallmarks of mammalian hearing. For example, genetic modifications of TECTA and TECTB, which are principal proteins that comprise the tectorial membrane (TM), have been shown to alter auditory thresholds and frequency tuning in ways that can be understood in terms of changes in the mechanical properties of the TM. Here, we investigate effects of genetic modification targeting CEACAM16, a third important TM protein. Loss of CEACAM16 has been recently shown to lead to progressive reductions in sensitivity. Whereas age-related hearing losses have previously been linked to changes in sensory receptor cells, the role of the TM in progressive hearing loss is largely unknown. Here, we show that TM stiffness and viscosity are significantly reduced in adult mice that lack functional CEACAM16 relative to age-matched wild-type controls. By contrast, these same mechanical properties of TMs from juvenile mice that lack functional CEACAM16 are more similar to those of wild-type mice. Thus, changes in hearing phenotype align with changes in TM material properties and can be understood in terms of the same TM wave properties that were previously used to characterize modifications of TECTA and TECTB. These results demonstrate that CEACAM16 is essential for maintaining TM mechanical and wave properties, which in turn are necessary for sustaining the remarkable sensitivity and selectivity of mammalian hearing with increasing age.
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spelling mit-1721.1/1435402023-01-30T16:46:06Z Age-related degradation of tectorial membrane dynamics with loss of CEACAM16 Mansour, Amer Sellon, Jonathan B Filizzola, Daniel Ghaffari, Roozbeh Cheatham, Mary Ann Freeman, Dennis M Massachusetts Institute of Technology. Research Laboratory of Electronics Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Studies of genetic disorders of sensorineural hearing loss have been instrumental in delineating mechanisms that underlie the remarkable sensitivity and selectivity that are hallmarks of mammalian hearing. For example, genetic modifications of TECTA and TECTB, which are principal proteins that comprise the tectorial membrane (TM), have been shown to alter auditory thresholds and frequency tuning in ways that can be understood in terms of changes in the mechanical properties of the TM. Here, we investigate effects of genetic modification targeting CEACAM16, a third important TM protein. Loss of CEACAM16 has been recently shown to lead to progressive reductions in sensitivity. Whereas age-related hearing losses have previously been linked to changes in sensory receptor cells, the role of the TM in progressive hearing loss is largely unknown. Here, we show that TM stiffness and viscosity are significantly reduced in adult mice that lack functional CEACAM16 relative to age-matched wild-type controls. By contrast, these same mechanical properties of TMs from juvenile mice that lack functional CEACAM16 are more similar to those of wild-type mice. Thus, changes in hearing phenotype align with changes in TM material properties and can be understood in terms of the same TM wave properties that were previously used to characterize modifications of TECTA and TECTB. These results demonstrate that CEACAM16 is essential for maintaining TM mechanical and wave properties, which in turn are necessary for sustaining the remarkable sensitivity and selectivity of mammalian hearing with increasing age. 2022-06-22T16:55:18Z 2022-06-22T16:55:18Z 2021 2022-06-22T16:50:26Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/143540 Mansour, Amer, Sellon, Jonathan B, Filizzola, Daniel, Ghaffari, Roozbeh, Cheatham, Mary Ann et al. 2021. "Age-related degradation of tectorial membrane dynamics with loss of CEACAM16." Biophysical Journal, 120 (21). en 10.1016/J.BPJ.2021.09.029 Biophysical Journal Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier
spellingShingle Mansour, Amer
Sellon, Jonathan B
Filizzola, Daniel
Ghaffari, Roozbeh
Cheatham, Mary Ann
Freeman, Dennis M
Age-related degradation of tectorial membrane dynamics with loss of CEACAM16
title Age-related degradation of tectorial membrane dynamics with loss of CEACAM16
title_full Age-related degradation of tectorial membrane dynamics with loss of CEACAM16
title_fullStr Age-related degradation of tectorial membrane dynamics with loss of CEACAM16
title_full_unstemmed Age-related degradation of tectorial membrane dynamics with loss of CEACAM16
title_short Age-related degradation of tectorial membrane dynamics with loss of CEACAM16
title_sort age related degradation of tectorial membrane dynamics with loss of ceacam16
url https://hdl.handle.net/1721.1/143540
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