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Dynamic study of tip-link tension and stereocilia motion in cochlea

Xu Xu Ma Wen-Kai Yao Wen-Juan

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Dynamic study of tip-link tension and stereocilia motion in cochlea

Xu Xu, Ma Wen-Kai, Yao Wen-Juan
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  • Explanation of cochlear active acoustic amplification mechanism has been an unsolved medical problem. This mechanism is closely related to the motion of the stereocilia at the top of the outer hair cells in the cochlea. The motion of stereocilia is regulated by the tip-link tension and the fluid force of the lymph fluid. Therefore, studying the tip-link tension during the motion of stereocilia is an important part of the explanation of the cochlea's active sensory sound amplification mechanism. Most of previous studies regarded the stereocilia as rigid bodies, and ignored the influence of shaft bending when studying the mechanical properties of hair bundle. Most of the researches on elastic stereocilia used the finite element simulation, or simplified the model by ignoring the fluid-solid coupling with lymph fluid, or considered only static loading. Based on the Poiseuille flow combined with the distributed parameter model, the analytical solution of the elastic motion of stereocilia is derived in this work. The dynamic response of the stereocilia under the shear force of the tectorial membrane and the change law of tip-link tension are studied. The shaft bending produces a nonlinear accumulation of displacement at the height of the stereocilia. The higher the stereocilia, the more obvious the accumulation effect is. Under the action of dynamic load, the shaft bending contributes most to the displacement response in the tall stereocilium, and this contribution is easily affected by frequency change. Under low frequency load, the displacement response of tall stereocilium comes mainly from the root deflection. At high frequency, the shaft bending increases significantly, and the displacement response is produced by the combination of shaft bending and root deflection. The change of F-actin content in the cochlea exposed to noise would affect the stereocilia stiffness. In this paper, it is found that the decrease of stereociliary Young's modulus will increase the peak value of normalized tension and reduce its peak frequency, and the amplitude of normalized tension will increase under the low frequency shear load. Since the tip-link is connected to an ion channel, the change of normalized tension will affect the probability of ion channels opening, change the ability of cochlea to perceive the sound of corresponding frequency, and then affect the frequency selectivity of hair bundle. Therefore, previous studies of stereocilia regarded as rigid bodies underestimated the response of the cochlea to low-frequency acoustic signals. This model accurately describes the law of tip-link tension and provides a corresponding theoretical explanation for hearing impairment caused by noise environment. Previous experiments have shown that the lymphatic viscous resistance has little effect on the deflection of stereocilia. In this paper, when the viscous resistance is ignored, the tip-link tension changes very little, and when the pressure between the stereocilia is ignored, the tip-link tension changes significantly and the resonance peak of $ {f_2} $ disappears. Therefore, lymphatic fluid regulates the resonance properties of the tip-link tension by creating the pressure between the stereocilia. The presence of lymphatics is essential for generating the frequency characteristics of the hair bundle. In the low frequency domain, the motion of stereocilia is regulated mainly by tip-link, and in the high frequency domain, it is regulated mainly by lymphatic pressure.
      Corresponding author: Yao Wen-Juan, wjyao@shu.edu.cn
    • Funds: Project supported by the Key Program of the National Natural Science Foundation of China (Grant No. 11932010)
    [1]

    Colantonio J R, Vermot J, Wu D, Langenbacher A D, Fraser S, Chen J N, Hill K L 2009 Nature 457 205Google Scholar

    [2]

    Pickles J O, Comis S D, Osborne M P 1984 Hearing Res. 15 103Google Scholar

    [3]

    Auer M, Koster A, Ziese U, Bajaj C, Volkmann N, Wang D, Hudspeth A 2008 J. Assoc. Res. Otolaryngol. 9 215Google Scholar

    [4]

    Assad J A, Shepherd G M, Corey D P 1991 Neuron 7 985Google Scholar

    [5]

    Tobin M, Chaiyasitdhi A, Michel V, Michalski N, Martin P 2019 eLife 8 e43473Google Scholar

    [6]

    Maoiléidigh D Ó, Jülicher F 2010 J. Acoust. Soc. Am. 128 1175Google Scholar

    [7]

    Fettiplace R, Crawford A C Evans M G 1992 Ann. N. Y. Acad. Sci. 656 1Google Scholar

    [8]

    Beurg M, Fettiplace R, Nam J H, Ricci A J 2009 Nat. Neurosci. 12 553Google Scholar

    [9]

    Furness D N, Hackney C M, Evans M G 2010 J. Physiol. 588 765Google Scholar

    [10]

    Park J, Wei G W 2013 J. Comput. Neurosci. 35 231Google Scholar

    [11]

    Jaramillo F, Hudspeth A J 1993 PNAS 90 1330Google Scholar

    [12]

    Lim K, Park S 2009 J. Biomech. 42 2158Google Scholar

    [13]

    Kachar B, Parakkal M, Kurc M, Zhao Y, Gillespie P 2000 PNAS 97 13336Google Scholar

    [14]

    Kazmierczak P, Sakaguchi H, Tokita J, Wilson-Kubalek E M, Milligan R A 2007 Nature 449 87Google Scholar

    [15]

    Ge J P, Elferich J, Goehring A, Zhao J, Gouaux E 2018 eLife 7 e38770Google Scholar

    [16]

    Richardson G P, Petit C 2019 Cold Spring Harbor Perspect. Med. 9 a033142Google Scholar

    [17]

    Dionne G, Qiu X F, Rapp M, Liang X P, Zhao B, Peng G H, Katsamba P S, Ahlsen G, Rubinstein R, Potter C S, Carragher B, Honig B, Müller U, Shapiro L 2018 Neuron 99 480Google Scholar

    [18]

    Bartsch T F, Hengel F E, Oswald A, Dionne G, Chipendo I V, Mangat S S, El Shatanofy M, Shapiro L, Müller U, Hudspeth A J 2019 PNAS 116 11048Google Scholar

    [19]

    Duncan R K, Grant J W 1997 Hearing Res. 104 15Google Scholar

    [20]

    Cotton J, Grant W 2004 Hearing Res. 197 96Google Scholar

    [21]

    Cotton J, Grant W 2004 Hearing Res. 197 105Google Scholar

    [22]

    Nam J H, Cotton J R, Grant J W 2005 J. Vestib. Res. 15 263Google Scholar

    [23]

    Tilney L G, Tilney M S 1986 Hearing Res. 22 55Google Scholar

    [24]

    You L, Cowin S C, Schaffler M B, Weinbaum S 2001 J. Biomech. 34 1375Google Scholar

    [25]

    Han Y F, Cowin S C, Schaffler M B, Weinbaum S 2004 PNAS 101 16689Google Scholar

    [26]

    Lin H W, Schneider M E, Kachar B 2005 Curr. Opin. Cell Biol. 17 55Google Scholar

    [27]

    Hackney C M, Furness D N 1995 Am. J. Physiol. 268 1Google Scholar

    [28]

    Strelioff D, Flock A 1984 Hearing Res. 15 19Google Scholar

    [29]

    Furness D N, Zetes D E, Hackney C M 1997 Proc. Biol. Sci. 264 45Google Scholar

    [30]

    Gittes F, Mickey B, Nettleton J, Howard J 1993 J. Cell Biol. 120 923Google Scholar

    [31]

    Howard J, Hudspeth A J 1988 Neuron 1 189Google Scholar

    [32]

    Tsuprun V, Santi P 2002 J. Histochem. Cytochem. 50 493Google Scholar

    [33]

    Flock Å, Strelioff D 1984 Nature 310 597Google Scholar

    [34]

    Szymko Y M, Dimitri P S, Saunders J C 1992 Hearing Res. 59 241Google Scholar

    [35]

    Fridberger A, Tomo I, Ulfendahl M, Monvel J B 2006 PNAS 103 1918Google Scholar

    [36]

    Vlajkovic S M, Housley G D, Muñoz D J B, Robson S C, Sévigny J, Wang C J H, Thorne P R 2004 Neuroscience 126 763Google Scholar

    [37]

    Avinash G B, Nuttall A L, Raphael Y 1993 Hearing Res. 67 139Google Scholar

    [38]

    Murakoshi M, Yoshida N, Kitsunai Y, Iida K, Kumano S, Suzuki T, Kobayashi T, Wada H 2006 Brain Res. 1107 121Google Scholar

    [39]

    Kondrachuk A V 2006 Adv. Space Res. 38 1052Google Scholar

    [40]

    Kozlov A S, Baumgart J, Risler T, Versteegh C P, Hudspeth A J 2011 Nature 474 376Google Scholar

    [41]

    Verpy E, Leibovici M, Michalski N, Goodyear R J, Houdon C, Weil D, Richardson G P, Petit C 2011 J. Comp. Neurol. 519 194Google Scholar

  • 图 1  发束理论模型示意图

    Figure 1.  Schematic diagram of theoretical model of hair bundle.

    图 2  单根静纤毛根部转角计算模型

    Figure 2.  Calculation model of root rotation angle of a single stereocilia.

    图 3  发束横断面图 (a)压力分布的位置; (b)相邻立体纤毛之间的淋巴流线

    Figure 3.  Top view of hair bundle: (a) The position of the pressure distribution; (b) lymphatic streamlines between adjacent stereocilia.

    图 4  单根静纤毛刚度

    Figure 4.  Stiffness of single stereocilium.

    图 5  静纤毛顶端位移比随频率的变化曲线

    Figure 5.  Variation curve of displacement ratio of the top of stereocilia with frequency.

    图 6  不同杨氏模量下tip-link归一化张力随频率的变化曲线 (a)$ {f_1} $; (b) $ {f_2} $

    Figure 6.  Variation curves of tip-link normalized tension with frequency under different Young's modulus: (a) f1; (b) f2.

    图 7  不同流体作用方式下归一化张力随频率的变化曲线 (a)$ {f_1} $; (b)$ {f_2} $

    Figure 7.  Variation curve of normalized tension with frequency under different fluid action modes: (a)$ {f_1} $; (b) $ {f_2} $.

    图 8  A和B处的压强 (a) A和B在发束中的位置; (b) A和B处压强随频率的变化曲线

    Figure 8.  The pressure at A and B: (a) The position of A and B in the hair bundle; (b) the variation curve of pressure at A and B.

    表 1  模型参数

    Table 1.  Model parameters.

    参数名称参数值
    静纤毛高度($l_1 $, $l_2 $, $l_3 $)/μm6.0, 2.8, 1.4
    静纤毛底圆锥高度($l_{{\rm{a}}1} $, $l_{{\rm{a}}2} $, $l_{{\rm{a}}3} $)/μm1.6, 1.0, 0.6
    高, 中静纤毛侧壁上tip-link
    连接点高度($l_{{\rm{t}}1} $, $l_{{\rm{t}}2} $)/μm
    3.0, 1.6
    圆柱体半径(r)/nm150
    圆锥最小半径(ra)/nm60
    相邻静纤毛间距(h0)/nm50
    静纤毛体均布质量(m)/(kg·m–1)8.48 × 10–11
    静纤毛杨氏模量(E)/GPa1.2
    淋巴液粘度系数(c = μ)/(Pa·s)6.59 × 10–4
    tip-link轴与水平面夹角(β1 = β2)π/4
    tip-link弹性常数(ktip1 = ktip2)/(N·m–1)5.3 × 10–4
    DownLoad: CSV

    表 2  静刚度的实验值与解析值

    Table 2.  Experimental value and analytical value of static stiffness

    实验值静刚度/
    (10–4 N·m–1)
    本模型计算的静
    刚度/(10–4 N·m–1)
    Flock and Strelioff[33] (1984)7.8 ± 2.26.25
    Szymko et al.[34] (1992)5.04 ± 2.68
    DownLoad: CSV
  • [1]

    Colantonio J R, Vermot J, Wu D, Langenbacher A D, Fraser S, Chen J N, Hill K L 2009 Nature 457 205Google Scholar

    [2]

    Pickles J O, Comis S D, Osborne M P 1984 Hearing Res. 15 103Google Scholar

    [3]

    Auer M, Koster A, Ziese U, Bajaj C, Volkmann N, Wang D, Hudspeth A 2008 J. Assoc. Res. Otolaryngol. 9 215Google Scholar

    [4]

    Assad J A, Shepherd G M, Corey D P 1991 Neuron 7 985Google Scholar

    [5]

    Tobin M, Chaiyasitdhi A, Michel V, Michalski N, Martin P 2019 eLife 8 e43473Google Scholar

    [6]

    Maoiléidigh D Ó, Jülicher F 2010 J. Acoust. Soc. Am. 128 1175Google Scholar

    [7]

    Fettiplace R, Crawford A C Evans M G 1992 Ann. N. Y. Acad. Sci. 656 1Google Scholar

    [8]

    Beurg M, Fettiplace R, Nam J H, Ricci A J 2009 Nat. Neurosci. 12 553Google Scholar

    [9]

    Furness D N, Hackney C M, Evans M G 2010 J. Physiol. 588 765Google Scholar

    [10]

    Park J, Wei G W 2013 J. Comput. Neurosci. 35 231Google Scholar

    [11]

    Jaramillo F, Hudspeth A J 1993 PNAS 90 1330Google Scholar

    [12]

    Lim K, Park S 2009 J. Biomech. 42 2158Google Scholar

    [13]

    Kachar B, Parakkal M, Kurc M, Zhao Y, Gillespie P 2000 PNAS 97 13336Google Scholar

    [14]

    Kazmierczak P, Sakaguchi H, Tokita J, Wilson-Kubalek E M, Milligan R A 2007 Nature 449 87Google Scholar

    [15]

    Ge J P, Elferich J, Goehring A, Zhao J, Gouaux E 2018 eLife 7 e38770Google Scholar

    [16]

    Richardson G P, Petit C 2019 Cold Spring Harbor Perspect. Med. 9 a033142Google Scholar

    [17]

    Dionne G, Qiu X F, Rapp M, Liang X P, Zhao B, Peng G H, Katsamba P S, Ahlsen G, Rubinstein R, Potter C S, Carragher B, Honig B, Müller U, Shapiro L 2018 Neuron 99 480Google Scholar

    [18]

    Bartsch T F, Hengel F E, Oswald A, Dionne G, Chipendo I V, Mangat S S, El Shatanofy M, Shapiro L, Müller U, Hudspeth A J 2019 PNAS 116 11048Google Scholar

    [19]

    Duncan R K, Grant J W 1997 Hearing Res. 104 15Google Scholar

    [20]

    Cotton J, Grant W 2004 Hearing Res. 197 96Google Scholar

    [21]

    Cotton J, Grant W 2004 Hearing Res. 197 105Google Scholar

    [22]

    Nam J H, Cotton J R, Grant J W 2005 J. Vestib. Res. 15 263Google Scholar

    [23]

    Tilney L G, Tilney M S 1986 Hearing Res. 22 55Google Scholar

    [24]

    You L, Cowin S C, Schaffler M B, Weinbaum S 2001 J. Biomech. 34 1375Google Scholar

    [25]

    Han Y F, Cowin S C, Schaffler M B, Weinbaum S 2004 PNAS 101 16689Google Scholar

    [26]

    Lin H W, Schneider M E, Kachar B 2005 Curr. Opin. Cell Biol. 17 55Google Scholar

    [27]

    Hackney C M, Furness D N 1995 Am. J. Physiol. 268 1Google Scholar

    [28]

    Strelioff D, Flock A 1984 Hearing Res. 15 19Google Scholar

    [29]

    Furness D N, Zetes D E, Hackney C M 1997 Proc. Biol. Sci. 264 45Google Scholar

    [30]

    Gittes F, Mickey B, Nettleton J, Howard J 1993 J. Cell Biol. 120 923Google Scholar

    [31]

    Howard J, Hudspeth A J 1988 Neuron 1 189Google Scholar

    [32]

    Tsuprun V, Santi P 2002 J. Histochem. Cytochem. 50 493Google Scholar

    [33]

    Flock Å, Strelioff D 1984 Nature 310 597Google Scholar

    [34]

    Szymko Y M, Dimitri P S, Saunders J C 1992 Hearing Res. 59 241Google Scholar

    [35]

    Fridberger A, Tomo I, Ulfendahl M, Monvel J B 2006 PNAS 103 1918Google Scholar

    [36]

    Vlajkovic S M, Housley G D, Muñoz D J B, Robson S C, Sévigny J, Wang C J H, Thorne P R 2004 Neuroscience 126 763Google Scholar

    [37]

    Avinash G B, Nuttall A L, Raphael Y 1993 Hearing Res. 67 139Google Scholar

    [38]

    Murakoshi M, Yoshida N, Kitsunai Y, Iida K, Kumano S, Suzuki T, Kobayashi T, Wada H 2006 Brain Res. 1107 121Google Scholar

    [39]

    Kondrachuk A V 2006 Adv. Space Res. 38 1052Google Scholar

    [40]

    Kozlov A S, Baumgart J, Risler T, Versteegh C P, Hudspeth A J 2011 Nature 474 376Google Scholar

    [41]

    Verpy E, Leibovici M, Michalski N, Goodyear R J, Houdon C, Weil D, Richardson G P, Petit C 2011 J. Comp. Neurol. 519 194Google Scholar

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Publishing process
  • Received Date:  10 June 2021
  • Accepted Date:  23 October 2021
  • Available Online:  10 February 2022
  • Published Online:  20 February 2022

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