# Probing how hair bundle mechanical properties shape the mechanotransducer receptor current

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $664,247

## Abstract

Abstract: Auditory and vestibular sensory cells use the hair bundle, a stair-cased array of actin filled
stereocilia, to translate mechanical motion into an electrical signal. Mechanically-gated (MET) ion channels
located at the tips of shorter stereocilia are activated by force created by the pulling of a tip link that extends
between stereocilia. As sensory hair bundles are a major site for both genetic disorders like Ushers syndrome
and are also susceptible to damage from noise and aging, understanding how these bundles operate is critical
to designing therapies for prevention and restoration of function. Mammalian cochlear hair bundles have unusual
morphologies and interstereocilia connectivity that is not as tight as other inner ear end organs. There is
considerable debate as to the mechanisms underlying processes impacting MET currents and hair bundle
mechanics, like fast and slow adaptation, gating compliance and voltage driven responses. There is further
controversy over whether we truly have causal links between MET current responses and mechanical, molecular
mechanisms. Before being able to use the power of genetic manipulation of newly identified MET molecules, we
need a clear understanding of hair bundle biophysical properties and how they impact MET receptor currents.
We hypothesize that the lack of connectivity in bundle motion is to optimize the hair bundle's response to natural
stimulation and that synchronization of stereocilia comes from the tectorial membrane (OHCs) or the fluid
stimulation (IHCs). We further hypothesize that we will identify mechanical correlates for fast and slow adaptation
as well as gating compliance; however, we do expect there to be less slow adaptation as compared to other hair
cell types but also that the mechanism of slow adaptation will not align with classical theories. And finally. we
hypothesize that MET channel properties work with hair bundle mechanics to create tuning of the receptor
current. We will investigate each of these hypotheses in the following specific aims. SA1 will generate a
comprehensive data set of MET channel and hair bundle properties at multiple frequency positions from rats and
mice P10-12 of age. By taking advantage of three modes of stimulations, wide probe, fluid jet and the newly
developed narrow probe, we can separate between MET channel and hair bundle properties. SA2 will directly
address hair bundle mechanics and known hair bundle properties using the newly developed high-speed imaging
with either narrow probe or fluid jet technology. Experiments will target MET channel gating compliance, fast and
slow adaptation and voltage dependent mechanical hair bundle responses. SA3 will generate frequency
response curves under physiological conditions using the wide probe and fluid jet to define the filtering properties
of the channel and the hair bundle. Completion of these aims will provide an unprecedented level of quantitative
information as to how the hair bundle moves and ...

## Key facts

- **NIH application ID:** 10778103
- **Project number:** 1R01DC021448-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Anthony J Ricci
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $664,247
- **Award type:** 1
- **Project period:** 2023-09-18 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10778103

## Citation

> US National Institutes of Health, RePORTER application 10778103, Probing how hair bundle mechanical properties shape the mechanotransducer receptor current (1R01DC021448-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10778103. Licensed CC0.

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