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Structural and Computational Biology and Molecular Biophysics

Houston, Texas

A BCM research lab.
Structural and Computational Biology & Molecular Biophysics
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William Brownell, Ph.D.

William Brownell, Ph.D.Jake and Nina Kamin Chair and Professor, Otolaryngology-Head & Neck Surgery

SCBMB Executive Committee Member

Baylor College of Medicine

Education:

S.B. Physics, University of Chicago (1968)
Ph.D. Physiology, University of Chicago (1973)

Research Interests:

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
  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 ionic currents, and membrane electromechanics. 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 mophometric data, extract elastic moduli of the different cell structures, and clarify ionic and molecular pathways within the cell.

Selected Publications:

  • Farrell B, Qian F, Kolomeisky A, Anvari B and Brownell WE. Measuring forces at the leading edge: a force assay for cell motility. Integr Biol (Camb), 5(1):204-14 (2013). PubMed
  • Corbitt C, Farinelli F, Brownell WE and Farrell B. Tonotopic relationships reveal the charge density varies along the lateral wall of outer hair cells. Biophys J, 102(12):2715-24 (2012). PubMed
  • Brownell WE, Jacob S, Hakizimana P, Ulfendahl M and Fridberger A. Membrane cholesterol modulates cochlear electromechanics. Pflugers Arch, 461(6):677-86 (2011). PubMed
  • Brownell WE, Qian F and Anvari B. Cell membrane tethers generate mechanical force in response to electrical simulation. Biophys J, 99(3):845-52 (2010). PubMed
  • Rajagopalan L, Organ-Darling LE, Liu H, Davidson AL, Raphael RM, Brownell WE and Pereira FA. Glycosylation regulates prestin cellular activity. J Assoc Res Otolarylgol, 11(1):39-51 (2010). PubMed
  • Brownell WE. WITHDRAWN: Membrane-based amplification in hearing. Hear Res, [Epub ahead of print] (2009). PubMed
  • Gliko O, Saggau P and Brownell WE. Compartmentalization of the outer hair cell demonstrated by slow diffusion in the extracisternal space. Biophys J, 97(4):1215-24 (2009). PubMed

For more publications, see listing on PubMed.

Contact Information:

Department: Bobby R. Alford Department of Otorhinolaryngology & Communicative Science
Address: Room NA505
Baylor College of Medicine
One Baylor Plaza
Houston, Texas 77030
Phone: 713-798-8540
Fax: 713-798-8553
E-mail: brownell@bcm.edu
Additional Links: Cochlear Biophysics Laboratory

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