About the Lab
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 membrane 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:
- The plasma membrane
- A highly organized cortical lattice made up of cytoskeletal proteins
- 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.
Brownell WE, Jacob S, Hakizimana P, Ulfendahl M, Fridberger A. Membrane cholesterol modulates cochlear electromechanics. Pflugers Arch 2011;461:677-86.
Nilsen N, Brownell WE, Sun SX, Spector AA. Effect of membrane mechanics on charge transfer by the membrane protein prestin. Biomech Model Mechanobiol 2011 Mar 2 [Epub ahead of print].
Brownell WE, Qian F, Anvari B. Cell membrane tethers generate mechanical force in response to electrical stimulation. Biophys J 2010;99:845-52.
Ashmore J, Avan P, Brownell WE, Dallos P, Dierkes K, Fettiplace R, Grosh K, Hackney CM, Hudspeth AJ, Jülicher F, Lindner B, Martin P, Meaud J, Petit C, Sacchi JR, Canlon B. The remarkable cochlear amplifier. Hear Res 2010;266:1-17.
Harland B, Brownell WE, Spector AA, Sun SX. Voltage-induced bending and electromechanical coupling in lipid bilayers. Phys Rec E Stat Nonlin Soft Matter Phys 2010;81:0310907.
Rajagopalan L, Organ-Darling LE, Liu H, Davidson AL, Raphael RM, Brownell WE, Pereira FA. Glycosylation regulates prestin cellular activity. J Assoc Res Otolaryngol 2010;11:39-51.