The remarkable sensitivity of mammalian hearing results from the ability of inner ear sensory receptor cells (called outer hair cells) to generate mechanical force in response to small electric fields. These forces can follow electrical signals up to 100 kHz and cause cell length changes that are easily seen when the cell is isolated from the cochlea. The mechanism responsible for this electromotility is a membrance based motor that resides in the cell's lateral wall. The lateral wall is a composite structure with nanoscale dimensions. Three layers are found within 100 nm of the cell's surface: 1) the plasma membrane; 2) a highly organized cortical lattice made up of cytoskeletal proteins, and 3) a novel subcellular organelle called the subsurface cisterna. This trilaminate organization is unique to the outer hair cell as is electromotility. We have developed techniques to selectively label and functionally dissect the layers. The nature of lipid-protein interactions in the two membranous layers is of particular interest. The contribution of each layer to the cell's electrical and mechanical anatomy is measured and computational models developed. Outer hair cells are investigated in vitro and subjected to a variety of mechanical, electrical, and chemical stimuli. Video-enhanced, confocal-laser-scanning, and atomic-force microscopy and optical tweezers are used to measure lateral diffusion in membranes, cell movements, membrane potentials and pH. Intracellular microelectrodes, patch clamp techniques, suction electrodes and voltage- and ligand-sensitive dyes are used to investigate the electroanatomy of cells including the ion channels found in the cell's different membrane domains. Analytic and numerical models are used to analyze morphometric data, extract elastic moduli of the different cell structures, and clarify ionic and molecular pathways within the cell.
Selected Publications:
Brownell, W.E. On the origins of outer hair cell electromotility. Hair Cell Micromechanics and Otoacoustic Emissions, edited by C.I. Berlin, L.J. Hood, a.J. Ricci. Delmar-Thomson Learning, Albany. NY, pp. 25-47, 2002.
Li, Z., Anvari, B., Takashima, M., Brecht, P., Torres, J.H., Brownell, W.E. Membrane tether formation from outer hair cells with optical tweezers. Biophysical Journal 82: 1386-1395, 2002.
Morimoto, N., Raphael, R.M., Nygren, A., Brownell, W.E. Excess plasma membrance and effects of ionic amphipaths on the mechanics of the outer hair cell lateral wall. American Journal of Physiology - Cell Physiology 282: C1076-1086, 2002.
Brownell, W.E., Spector, A.A., Raphael, R.M., Popel, A.S. Micro- and nanomechanics of the cochlear outer hair cell. Ann Rev of Biomedical engineering 3: 169-194, 2001.
Lue, A.J.-C., Zhao, H-B., Brownell, W.E. Chlorpromazine alters outer hair cell electromotility. Otolaryngology - Head and Neck Surgery 125:71-76. 2001.
Oghalai, J.S., Holt, J.R., Nakagawa, T., Jung, T.M., Coker, N.J., Jenkins, H.A., Eatock, R.A., and Brownell W.E. Harvesting human hair cells. Ann. Otol. Rhinol. Laryngol. 109: 9-16, 2000.
Oghalai, J.S., Zhao, H.-B., Kutz, J.W., and Brownell, W.E. Voltage- and tension-dependent lipid mobility in the outer hair cell plasma membrane. Science 287: 658-661, 2000.
Raphael, R.M., Popel, A.S., Brownell, W.E. A membrane bending model of outer hair cell electromotiligy. Biophysical J 78: 2844-2862, 2000.
Ratnanather, J.T., Popel, A.S., Brownell, W.E. An analysis of the hydraulic conductivity of the extracisternal space of the cochlear outer hair cell. Journal of Mathematical Biology 40: 372-382, 2000.
Brownell, W.E. How the Ear Works - Nature's Solutions For Listening. Volta Review, 99:9-28, 1999 .
Lue A.J., Brownell W.E. Salicylate induced changes in outer hair cell lateral wall stiffness. Hearing Research 135(1-2):163-8, 1999
Oghalai, J.S., Tran, T.D., Raphael, R.M., Nakagawa, T., Brownell, W.E. Transverse and lateral mobility in outer hair cell lateral wall membranes. Hearing Research 135: 19-28, 1999.
Spector, A.A., Brownell, W.E., Popel, A.S. Nonlinear active force generation by cochlear outer hair cell. J. Acoust. Soc. Am., 105:2414-2420, 1999.
Brownell, W.E., Popel, A.S. Electrical and mechanical anatomy of the outer hair cell. Psychophysical and Physiological Advances in Hearing, edited by A.R. Palmer, A. Rees, A.Q. Summerfield, R. Meddis. London: Whurr Publishers, London pp. 89-96, 1998.
Nguyen, T-V. N., Brownell, W.E. Contribution of membrane cholesterol to outer hair cell lateral wall stiffness. Otolaryngology - Head and Neck Surgery 119:14-20, 1998.
Oghalai, J.S., Holt, J.R., Nakagawa, T., Jung, T.M., Coker, N.J., Jenkins, H.A., Eatock, R.A., Brownell, W.E. Ionic currents and electromotility in human hair cells. J. Neurophysiology 79:2235-2239, 1998.
Oghalai, J.S., Patel, A.A., Nakagawa, T., Brownell, W.E. Fluorescence-Imaged Microdeformation of the Outer Hair Cell Lateral Wall. J. Neuroscience, 18:48-58, 1998.
Halter, J.A., Kruger, R.P., Yium, M.J., Brownell, W.E. The influence of the subsurface cisterna on the electrical properties of the outer hair cell. Neuroreport 8: 2517-2521, 1997.
Sit, P.S., Spector, A.A., Lue, A.J., Popel, A.S., and Brownell, W.E. Micropipet aspiration on the outer hair cell lateral wall. Biophysical Journal 72: 2812-2819, 1997.
