Effects of chlorpromazine on mechanical properties of the
outer hair cell plasma membrane
David R. Murdock 1*, Sergey Ermilov 1, Alexander A. Spector 2, Aleksander S. Popel 2, William E. Brownell 3 and Bahman Anvari 1
1 Rice University
2 The Johns Hopkins University
3 Baylor College of Medicine
* To whom correspondence should be addressed. E-mail: david.murdock{at}bcm.tmc.edu.
Submitted on July 5, 2005
Revised on August 17, 2005
Accepted on 20 September 2005
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Abstract |
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An optical tweezers system was used to characterize the effects of chlorpromazine (CPZ) on the mechanical properties of the mammalian outer hair cell (OHC) through the formation of plasma membrane (PM) tethers. Such tethers exhibited force relaxation when held at a constant length for several minutes. We used a 2nd order generalized Kelvin body to model tether force behavior from which several mechanical parameters were then calculated including stiffness, viscosity-associated measures, and force relaxation time constants. The results of the analysis portray a two-part relaxation process characterized by significantly different rates of force decay, which we propose is due to the local reorganization of lipids within the tether and the flow of external lipid area into the tether. We found that CPZ's effect was limited to the latter phenomenon since only the second phase of relaxation was significantly affected by the drug. This finding coupled with an observed large reduction in overall tether forces implies a common basis for the drug's effects, the PM-cytoskeleton interaction. The CPZ-induced changes in tether viscoelastic behavior suggest that alterations in the mechanical properties of the OHC lateral wall could play a role in the modulation of OHC electromotility by CPZ.
Key Words:
Kelvin body, amphipathic drugs, electromotility, laser tweezers, membrane tether
