In the mammalian auditory system, outer-hair-cell hair bundles (OHBs) transduce sound-induced forces into receptor currents. OHB receptor currents drive cochlear amplification, which is responsible for the high sensitivity and wide dynamic range of hearing. Although OHBs differ conspicuously in morphology from other types of bundles, we have a poor understanding of how OHB structure impacts OHB function. We show how the 3D morphology of an OHB impacts its mechanics and transduction. An OHB comprises about 100 rod-like stereocilia, which pivot on the surface of its sensory outer hair cell. Stereocilium pivot positions form columns and a V shape. We measure the pivot positions using STED microscopy and find that OHB columns are far from parallel. The far-from-parallel columns aspect of OHB morphology has been overlooked in prior work. To determine the effects of an OHB’s far-from-parallel columns and V shape, we build a mathematical model of an OHB, relating its pivot positions, 3D morphology, mechanics, and receptor current. The model is constrained by 19 experimental observations. By deforming the 3D morphology of the OHB in the model, we deduce how the OHB’s structure affects its function. The 3D morphology of the OHB halves its stiffness (doubling deflection sensitivity), doubles its damping coefficient, and causes stereocilium deflections driven by stimulus forces to differ considerably within the OHB. Stereocilium deflections cause the opening and closing of ion channels through which the receptor current flows. Owing to the stereocilium-deflection differences, the currents passing through the ion channels vary substantially across the OHB. Ultimately, the OHB’s 3D morphology increases its receptor-current dynamic range more than twofold. These results imply that pivot-position changes owing to development, mutations, or location within the mammalian auditory organ, greatly alter OHB function.
Zhu et al. (Sun,) studied this question.
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