Ji-wook Kim†‡§, Jae-Hyun Lee†‡§, Ji-Hyun Ma∥#, Eunna Chung†‡§, Hongsuh Choi†‡§, Jinwoong Bok∥⊥#, and Jinwoo Cheon*†‡§
† Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea
‡ Yonsei-IBS Institute, Yonsei University, Seoul 03722, Republic of Korea
§ Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea
∥Department of Anatomy, ⊥Department of Otorhinolaryngology, and #BK21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
J.-w.K., J.-H.L., and J.-H.M. contributed equally to this work.
Sound perception via mechano-sensation is a remarkably sensitive and fast transmission process, converting sound as a mechanical input to neural signals in a living organism. Although knowledge of auditory hair cell functions has advanced over the past decades, challenges remain in understanding their biomechanics, partly because of their biophysical complexity and the lack of appropriate probing tools. Most current studies of hair cells have been conducted in a relatively low-frequency range (＜1000 Hz); therefore, fast kinetic study of hair cells has been difficult, even though mammalians have sound perception of 20 kHz or higher. Here, we demonstrate that the magnetic force nanoprobe (MFN) has superb spatiotemporal capabilities to mechanically stimulate spatially-targeted individual hair cells with a temporal resolution of up to 9 μs, which is equivalent to approximately 50 kHz; therefore, it is possible to investigate avian hair cell biomechanics at different tonotopic regions of the cochlea covering a full hearing frequency range of 50 to 5000 Hz. We found that the variation of the stimulation frequency and amplitude of hair bundles creates distinct mechanical responsive features along the tonotopic axis, where the kinetics of the hair bundle recovery motion exhibits unique frequency-dependent characteristics: basal, middle, and apical hair bundles can effectively respond at their respective ranges of frequency. We revealed that such recovery kinetics possesses two different time constants that are closely related to the passive and active motilities of hair cells. The use of MFN is critical for the kinetics study of free-standing hair cells in a spatiotemporally distinct tonotopic organization.
Keywords: Magnetic nanoparticle; mechanical force; audio frequency; avian hair cell; tonotopy; bundle recovery time constant