# Molecules and Mechanisms of Mammalian Hair Cell Mechanotransduction

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $618,483

## Abstract

Abstract: A major first step in audition is the conversion of mechanical deflection of the sensory hair
bundle into an electrical signal that drives the hair cell receptor potential that in turn controls cochlear
amplification (outer hair cells) and synaptic transmission (inner hair cells). Alterations in any step of this
process will degrade signal processing throughout the auditory pathway. During the previous funding
period, we demonstrated that mammalian cochlea hair bundles do not move coherently, meaning that
there were both temporal and magnitude differences between stereocilia motion depending on the mode
of stimulation. The lack of coherence leads to very different mechanotransducer current responses, which
are predicted to generate very different receptor potentials. This finding drives a major component of the
present proposal which is focused upon identifying how hair bundles move in situ, to better understand
the properties of the physiologically driven mechanotransducer currents. We have developed new
technology including imaging bundle movement in situ at high speeds as well as image processing
algorithms that can detect motions at below 2 nm. We will use these new technologies as well as high
speed calcium imaging, new fluid jet and stiff probe stimulating devices and electrophysiological tools to
investigate stereocilia motion. Results from these experiments will shed light onto why outer hair cells
are embedded in the tectorial membrane and inner hair cells are not. We will also identify the hair bundle
and tectorial membrane mechanical properties responsible for regulating hair bundle motion. During the
past funding period we also identified several mechanisms by which the lipid membrane either directly or
indirectly alters mechanotransduction currents. We have developed new technologies including
fluorescence recovery after photobleaching to directly assess the mechanical properties of the lipid
bilayer as a means of identifying the underlying mechanisms for regulating the mechanotransducer
channel. We will use these new technologies coupled with pharmacological manipulations of the lipid
bilayer to investigate the role of specific lipids and their mechanical properties in modulating hair cell
MET.

## Key facts

- **NIH application ID:** 9850963
- **Project number:** 5R01DC003896-23
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Anthony J Ricci
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $618,483
- **Award type:** 5
- **Project period:** 1999-01-18 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850963

## Citation

> US National Institutes of Health, RePORTER application 9850963, Molecules and Mechanisms of Mammalian Hair Cell Mechanotransduction (5R01DC003896-23). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9850963. Licensed CC0.

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