Publications

Assistant Professor of Otolaryngology - Head & Neck Surgery (OHNS)

Publications

Links regulate deflection fluctuations in the sensory cells of hearing Physical Review E Marrocchio, R., Ó Maoiléidigh, D. 2025; 111: 034403 More

View details for DOI 10.1103/PhysRevE.111.034403
Gating-spring stiffness increases outer-hair-cell bundle stiffness, damping, and receptor current. Scientific reports Zhu, Z., Reid, W., Ó Maoiléidigh, D. 2024; 14 (1): 29904 More

Abstract

In our ears, outer-hair-cell bundles (OHBs) convert sound-induced forces into receptor currents that drive cochlear amplification, the process responsible for the micropascal-scale threshold and million-fold dynamic range of hearing. OHBs rely on gating springs to open mechanoelectrical-transduction (MET) ion channels, through which the receptor current flows. OHBs have larger gating-spring stiffnesses than other types of hair bundles, but we have a poor understanding of how gating-spring stiffness contributes to OHB mechanics and receptor-current regulation. Using experimentally-constrained mathematical models of the OHB, we show that the increased gating-spring stiffness in an OHB increases its stiffness and damping. The OHB's 3D morphology reduces the contribution of gating-spring stiffness to OHB stiffness, reduces the contribution of MET-channel gating to OHB stiffness and damping, but causes additional OHB damping that rises with gating-spring stiffness. Gating-spring stiffness increases the OHB's receptor current but decreases its displacement-current dynamic range. Strikingly, the OHB's 3D morphology causes its force-current dynamic range to decrease with gating-spring stiffness. Our results suggest a trade-off between threshold and dynamic range regulated by OHB gating-spring stiffness.

View details for DOI 10.1038/s41598-024-81355-5

View details for PubMedID 39622900

View details for PubMedCentralID 10801851
3D Morphology of an Outer-Hair-Cell Hair Bundle Increases Its Displacement and Dynamic Range. Biophysical journal Zhu, Z., Reid, W., George, S. S., Ou, V., Maoiléidigh, D. Ó. 2024 More

Abstract

In mammals, outer-hair-cell hair bundles (OHBs) transduce sound-induced forces into receptor currents and are required for the wide dynamic range and high sensitivity of hearing. OHBs differ conspicuously in morphology from other types of bundles. Here, we show that the 3D morphology of an OHB greatly impacts its mechanics and transduction. An OHB comprises rod-like stereocilia, which pivot on the surface of its sensory outer hair cell. Stereocilium pivot positions are arranged in columns and form a V shape. We measure the pivot positions and determine that OHB columns are far from parallel. To calculate the consequences of an OHB's V shape and far-from-parallel columns, we develop a mathematical model of an OHB that relates it pivot positions, 3D morphology, mechanics, and receptor current. We find that the 3D morphology of the OHB can halve its stiffness, can double its damping coefficient, and causes stereocilium displacements driven by stimulus forces to differ substantially across the OHB. Stereocilium displacements drive the opening and closing of ion channels through which the receptor current flows. Owing to the stereocilium-displacement differences, the currents passing through the ion channels can peak versus the stimulus frequency and vary considerably across the OHB. Consequently, the receptor current peaks versus the stimulus frequency. Ultimately, the OHB's 3D morphology can increase its receptor-current dynamic range more than twofold. Our findings imply that potential pivot-position changes owing to development, mutations, or location within the mammalian auditory organ might greatly alter OHB function.

View details for DOI 10.1016/j.bpj.2024.08.009

View details for PubMedID 39161094
The coherency of motion of two stereocilia depends on the viscoelastic properties of their link 15th International Mechanics of Hearing Workshop Marrocchio, R., Ó Maoiléidigh, D. Zenodo. 2024 More

View details for DOI 10.5281/zenodo.12613263
The 3D Morphology of the Outer-Hair-Cell Hair Bundle Causes Spatial Variation in Its Stereocilium Displacements and Channel Currents 15th International Mechanics of Hearing Workshop Zhu, Z., Ó Maoiléidigh, D. Zenodo. 2024 More

View details for DOI 10.5281/zenodo.13713542
Resting Calcium Dependence of the Outer Hair Cell Hair Bundle 15th International Mechanics of Hearing Workshop Chatterjee, R., Ó Maoiléidigh, D. Zenodo. 2024 More

View details for DOI 10.5281/zenodo.13730699
The Functional Contributions of Links in Mammalian Cochlear Hair Bundles 14th International Mechanics of Hearing Workshop Zhu, Z., Reid, W., Ó Maoiléidigh, D. 2024: 050008 More

View details for DOI 10.1063/5.0189205
Coupling between the stereocilia of rat sensory inner-hair-cell hair bundles is weak, shaping their sensitivity to stimulation. The Journal of neuroscience : the official journal of the Society for Neuroscience Scharr, A. L., Maoileidigh, D. O., Ricci, A. J. 2023 More

Abstract

The hair bundle is the universal mechanosensory organelle of auditory, vestibular, and lateral-line systems. A bundle comprises mechanically coupled stereocilia, whose displacements in response to stimulation activate a receptor current. The similarity of stereociliary displacements within a bundle regulates fundamental properties of the receptor current like its speed, magnitude, and sensitivity. However, the dynamics of individual stereocilia from the mammalian cochlea in response to a known bundle stimulus has not been quantified. We developed a novel high-speed system, which dynamically stimulates and tracks individual inner-hair-cell stereocilia from male and female rats. Stimulating 2-3 of the tallest stereocilia within a bundle (nonuniform stimulation) caused dissimilar stereociliary displacements. Stereocilia further from the stimulator moved less, but with little delay, implying that there is little slack in the system. Along the axis of mechanical sensitivity, stereocilium displacements peaked and reversed direction in response to a step stimulus. A viscoelastic model explained the observed displacement dynamics, which implies that coupling between the tallest stereocilia is effectively viscoelastic. Coupling elements between the tallest inner-hair-cell stereocilia were 2-3 times stronger than elements anchoring stereocilia to the cell's surface but were 10-10,000 times weaker than those of a well-studied non-cochlear hair bundle. Coupling was too weak to ensure that stereocilia move similarly in response to nonuniform stimulation at auditory frequencies. Our results imply that more uniform stimulation across the tallest stereocilia of an inner-hair-cell bundle in vivo is required to ensure stereociliary displacement similarity, increasing the speed, sensitivity, and magnitude of the receptor current.SIGNIFICANCE STATEMENT:Generation of the hair cell's receptor current is the first step in electrically encoding auditory information in the hearing organs of all vertebrates. The receptor current is shaped by mechanical coupling between stereocilia in each hair cell's hair bundle. Here we provide foundational information on the mechanical coupling between stereocilia of cochlear inner hair cells. In contrast to other types of hair cell, coupling between inner hair cell stereocilia is weak, causing slower, smaller, and less sensitive receptor currents in response to stimulation of few, rather than many, stereocilia. Our results imply that inner hair cells need many stereocilia to be stimulated in vivo to ensure fast, large, and sensitive receptor currents.

View details for DOI 10.1523/JNEUROSCI.1588-22.2023

View details for PubMedID 36746628
Dimensions of a Living Cochlear Hair Bundle Front Cell Dev Biol Miller, K. K., Atkinson, P., Mendoza, K., Ó Maoiléidigh, D., Grillet, N. 2021; 9: 742529 More

Abstract

The hair bundle is the mechanosensory organelle of hair cells that detects mechanical stimuli caused by sounds, head motions, and fluid flows. Each hair bundle is an assembly of cellular-protrusions called stereocilia, which differ in height to form a staircase. Stereocilia have different heights, widths, and separations in different species, sensory organs, positions within an organ, hair-cell types, and even within a single hair bundle. The dimensions of the stereociliary assembly dictate how the hair bundle responds to stimuli. These hair-bundle properties have been measured previously only to a limited degree. In particular, mammalian data are either incomplete, lack control for age or position within an organ, or have artifacts owing to fixation or dehydration. Here, we provide a complete set of measurements for postnatal day (P) 11 C57BL/6J mouse apical inner hair cells (IHCs) obtained from living tissue, tissue mildly-fixed for fluorescent imaging, or tissue strongly fixed and dehydrated for scanning electronic microscopy (SEM). We found that hair bundles mildly-fixed for fluorescence had the same dimensions as living hair bundles, whereas SEM-prepared hair bundles shrank uniformly in stereociliary heights, widths, and separations. By determining the shrinkage factors, we imputed live dimensions from SEM that were too small to observe optically. Accordingly, we created the first complete blueprint of a living IHC hair bundle. We show that SEM-prepared measurements strongly affect calculations of a bundle's mechanical properties - overestimating stereociliary deflection stiffness and underestimating the fluid coupling between stereocilia. The methods of measurement, the data, and the consequences we describe illustrate the high levels of accuracy and precision required to understand hair-bundle mechanotransduction.

View details for DOI 10.3389/fcell.2021.742529

View details for PubMedCentralID PMC8657763
A Bundle of Mechanisms: Inner-Ear Hair-Cell Mechanotransduction Trends in neurosciences Ó Maoiléidigh, D., Ricci, A. J. 2019; 42: 221-236