A membrane bending model of outer hair cell electromotility.

We propose a new mechanism for outer hair cell electromotility based on electrically induced localized changes in the curvature of the plasma membrane (flexoelectricity). Electromechanical coupling in the cell's lateral wall is modeled in terms of linear constitutive equations for a flexoelectric membrane and then extended to nonlinear coupling based on the Langevin function. The Langevin function, which describes the fraction of dipoles aligned with an applied electric field, is shown to be capable of predicting the electromotility voltage displacement function. We calculate the electrical and mechanical contributions to the force balance and show that the model is consistent with experimentally measured values for electromechanical properties. The model rationalizes several experimental observations associated with outer hair cell electromotility and provides for constant surface area of the plasma membrane. The model accounts for the isometric force generated by the cell and explains the observation that the disruption of spectrin by diamide reduces force generation in the cell. We discuss the relation of this mechanism to other proposed models of outer hair cell electromotility. Our analysis suggests that rotation of membrane dipoles and the accompanying mechanical deformation may be the molecular mechanism of electromotility.

[1]  R. Hochmuth,et al.  Membrane viscoplastic flow. , 1976, Biophysical journal.

[2]  J. Swanson,et al.  Cell membrane orientation visualized by polarized total internal reflection fluorescence. , 1999, Biophysical journal.

[3]  Hong-Bo Zhao,et al.  Voltage- and tension-dependent lipid mobility in the outer hair cell plasma membrane. , 2000, Science.

[4]  W. Helfrich,et al.  Measurement of the curvature-elastic modulus of egg lecithin bilayers. , 1976, Biochimica et biophysica acta.

[5]  G. Malinas Physical properties , 1973 .

[6]  S. BRODETSKY,et al.  Theory of Plates and Shells , 1941, Nature.

[7]  S. Takashima Computation of the dipole moment of protein molecules using protein databases.: Bacteriophage T4 lysozyme and its mutants , 1999 .

[8]  Renato Nobili,et al.  How well do we understand the cochlea? , 1998, Trends in Neurosciences.

[9]  J. Santos-Sacchi,et al.  Mapping the distribution of the outer hair cell motility voltage sensor by electrical amputation. , 1993, Biophysical journal.

[10]  A. T. Todorov,et al.  Flexoelectricity of lipid bilayers , 1990 .

[11]  J. Santos-Sacchi,et al.  On the frequency limit and phase of outer hair cell motility: effects of the membrane filter , 1992, Journal of Neuroscience.

[12]  W. H. Toliver,et al.  Liquid Crystals , 1912, Nature.

[13]  Robert B. Meyer,et al.  Piezoelectric Effects in Liquid Crystals , 1969 .

[14]  W. Helfrich Deformation of Lipid Bilayer Spheres by Electric Fields , 1974, Zeitschrift fur Naturforschung. Section C, Biosciences.

[15]  J. Santos-Sacchi,et al.  Harmonics of outer hair cell motility. , 1993, Biophysical journal.

[16]  Alexander G. Petrov,et al.  Flexoelectricity of Charged and Dipolar Bilayer Lipid Membranes Studied by Stroboscopic Interferometry , 1994 .

[17]  M. Ulfendahl,et al.  Ultrastructural correlates of inner ear sensory cell shortening. , 1988, Journal of submicroscopic cytology and pathology.

[18]  W. Brownell,et al.  Fluorescence-Imaged Microdeformation of the Outer Hair Cell Lateral Wall , 1998, The Journal of Neuroscience.

[19]  W Hemmert,et al.  Limiting dynamics of high-frequency electromechanical transduction of outer hair cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[20]  G. Oster,et al.  Curvature-mediated interactions between membrane proteins. , 1998, Biophysical journal.

[21]  W. Brownell,et al.  Micropipette aspiration on the outer hair cell lateral wall. , 1997, Biophysical journal.

[22]  W. Helfrich Elastic Properties of Lipid Bilayers: Theory and Possible Experiments , 1973, Zeitschrift fur Naturforschung. Teil C: Biochemie, Biophysik, Biologie, Virologie.

[23]  J. Ashmore The G.L. Brown Prize Lecture. The cellular machinery of the cochlea , 1994, Experimental physiology.

[24]  D. Boal,et al.  Simulations of the erythrocyte cytoskeleton at large deformation. I. Microscopic models. , 1998, Biophysical journal.

[25]  G. Pelzl Thermodynamic Behavior and Physical Properties of Thermotropic Liquid Crystals , 1994 .

[26]  Alexander G. Petrov,et al.  First observation of the converse flexoelectric effect in bilayer lipid membranes , 1994 .

[27]  K. Iwasa A membrane motor model for the fast motility of the outer hair cell. , 1994, The Journal of the Acoustical Society of America.

[28]  C. Steele,et al.  Mechanical properties of the lateral cortex of mammalian auditory outer hair cells. , 1996, Biophysical journal.

[29]  R. Waugh Elastic energy of curvature-driven bump formation on red blood cell membrane. , 1996, Biophysical journal.

[30]  W. E. Brownell,et al.  Concomitant salicylate-induced alterations of outer hair cell subsurface cisternae and electromotility , 1991, Journal of neurocytology.

[31]  R. Waugh,et al.  Bending rigidity of SOPC membranes containing cholesterol. , 1993, Biophysical journal.

[32]  J. Ashmore A fast motile response in guinea‐pig outer hair cells: the cellular basis of the cochlear amplifier. , 1987, The Journal of physiology.

[33]  Hendrikus Duifhuis,et al.  Biophysics of Hair Cell Sensory Systems , 1993 .

[34]  F. Mammano,et al.  The membrane-based mechanism of cell motility in cochlear outer hair cells. , 1998, Molecular biology of the cell.

[35]  F. Sachs,et al.  Voltage-dependent Membrane Displacements Measured by Atomic Force Microscopy , 1998, The Journal of general physiology.

[36]  J. Santos-Sacchi,et al.  Effects of Salicylate and Lanthanides on Outer Hair Cell Motility and Associated Gating Charge , 1996, The Journal of Neuroscience.

[37]  Peter Dallos,et al.  Nature of the motor element in electrokinetic shape changes of cochlear outer hair cells , 1991, Nature.

[38]  Marcelo Alonso,et al.  Mechanics and thermodynamics , 1980 .

[39]  W. Brownell,et al.  Transverse and lateral mobility in outer hair cell lateral wall membranes , 1999, Hearing Research.

[40]  D. Lim,et al.  Cell and molecular basis of hearing. , 1998, Kidney international. Supplement.

[41]  K. Iwasa,et al.  Electrically driven motor in the outer hair cell: effect of a mechanical constraint. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Ashmore Jf The G.L. Brown Prize Lecture. The cellular machinery of the cochlea , 1994 .

[43]  K. Iwasa,et al.  Effect of diamide on force generation and axial stiffness of the cochlear outer hair cell. , 1997, Biophysical journal.

[44]  W. C. Hwang,et al.  Energy of dissociation of lipid bilayer from the membrane skeleton of red blood cells. , 1997, Biophysical journal.

[45]  Craig C. Bader,et al.  Evoked mechanical responses of isolated cochlear outer hair cells. , 1985, Science.

[46]  Modulation of outer hair cell compliance and force by agents that affect hearing , 1997, Hearing Research.

[47]  R. Waugh,et al.  Accelerated interleaflet transport of phosphatidylcholine molecules in membranes under deformation. , 1996, Biophysical journal.

[48]  S Chien,et al.  An elastic network model based on the structure of the red blood cell membrane skeleton. , 1996, Biophysical journal.

[49]  A. Popel,et al.  Estimation of elastic moduli and bending stiffness of the anisotropic outer hair cell wall. , 1998, The Journal of the Acoustical Society of America.

[50]  K. Sung,et al.  Impaired echinocytic transformation of ankyrin‐ and spectrin‐deficient erythrocytes in mice , 1988, American journal of hematology.

[51]  W. Brownell,et al.  QUANTITATIVE ASSESSMENT OF DRUG-INDUCED CHANGE IN OHC LATERAL WALL MECHANICS , 2000 .

[52]  R. Waugh,et al.  Local and nonlocal curvature elasticity in bilayer membranes by tether formation from lecithin vesicles. , 1992, Biophysical journal.

[53]  J. Santos-Sacchi,et al.  Motility voltage sensor of the outer hair cell resides within the lateral plasma membrane. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[54]  J. Ashmore,et al.  The outer hair cell motor in membrane patches , 1997, Pflügers Archiv.

[55]  W. Webb,et al.  Thermal fluctuations of large cylindrical phospholipid vesicles. , 1984, Biophysical journal.

[56]  J. Santos-Sacchi,et al.  Reversible inhibition of voltage-dependent outer hair cell motility and capacitance , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[57]  K. Iwasa,et al.  A membrane-based force generation mechanism in auditory sensory cells. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[58]  In the cochlea , 1989 .

[59]  P Dallos,et al.  Outer hair cells: the inside story. , 1997, The Annals of otology, rhinology & laryngology. Supplement.

[60]  S Chien,et al.  Membrane model of endothelial cells and leukocytes. A proposal for the origin of a cortical stress. , 1995, Journal of biomechanical engineering.

[61]  M. Bloom,et al.  Physical properties of the fluid lipid-bilayer component of cell membranes: a perspective , 1991, Quarterly Reviews of Biophysics.

[62]  S. Lowen The Biophysical Journal , 1960, Nature.

[63]  Temperature-dependence of a fast motile response in isolated outer hair cells of the guinea-pig cochlea. , 1988, Quarterly journal of experimental physiology.

[64]  Jonathan E. Gale,et al.  An intrinsic frequency limit to the cochlear amplifier , 1997, Nature.

[65]  C. Smith,et al.  Ultrastructure of the organ of Corti. , 1968, Advancement of science.

[66]  A. Petrov Flexoelectric Model for Active Transport , 1975 .

[67]  M. D. Mitov,et al.  Mechanical properties of model membranes studied from shape transformations of giant vesicles. , 1998, Biochimie.

[68]  Frederick J. Milford,et al.  Foundations of Electromagnetic Theory , 1961 .

[69]  C. Steele,et al.  Orthotropic piezoelectric properties of the cochlear outer hair cell wall. , 1995, The Journal of the Acoustical Society of America.

[70]  Alan R. Palmer,et al.  Psychophysical and Physiological Advances in Hearing , 1998 .

[71]  A. Spector Nonlinear Electroelastic Model for the Composite Outer Hair Cell Wall , 1999, ORL.

[72]  Thomas Friedrich,et al.  KCNQ4, a Novel Potassium Channel Expressed in Sensory Outer Hair Cells, Is Mutated in Dominant Deafness , 1999, Cell.

[73]  A. Popel,et al.  Nonlinear active force generation by cochlear outer hair cell. , 1999, Journal of the Acoustical Society of America.

[74]  T. Reese,et al.  Regional specialization of the hair cell plasmalemma in the organ of corti , 1977, The Anatomical record.

[75]  D. Mountain,et al.  A piezoelectric model of outer hair cell function. , 1994, The Journal of the Acoustical Society of America.

[76]  Smith Ca Ultrastructure of the organ of Corti. , 1968 .

[77]  I.P. Kaminow,et al.  Principles and applications of ferroelectrics and related materials , 1978, Proceedings of the IEEE.

[78]  Tomonori Takasaka,et al.  Density of motility-related charge in the outer hair cell of the guinea pig is inversely related to best frequency , 1998, Neuroscience Letters.

[79]  Matthew C. Holley,et al.  Outer Hair Cell Motility , 1996 .

[80]  E. Sackmann,et al.  Measurement of erythrocyte membrane elasticity by flicker eigenmode decomposition. , 1995, Biophysical journal.

[81]  P Dallos,et al.  Theory of electrically driven shape changes of cochlear outer hair cells. , 1993, Journal of neurophysiology.

[82]  B. Kachar,et al.  Structure of the cortical cytoskeleton in mammalian outer hair cells. , 1992, Journal of cell science.