MOLECULAR SIMULATION OF AMPHIPHILE EFFECTS ON BIOLOGICAL MEMBRANE ELECTROSTATIC

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Salicylate, an amphiphilic molecule and a popular member of non-steroidal anti-inflammatory drug family, is known to affect hearing through reduction of the electromechanical coupling in the outer hair cells of the ear. Investigations into the effects of salicylate on electromotility, shape, and membrane capacitance of the outer hair cell of the ear have been pursued experimentally. However, the molecular mechanism of salicylate interaction with biological membranes and its effect on outer hair cell electrophysiology are still unknown. Our long term goal is to develop multiscale models of the outer hair cell in order to understand the molecular mechanism of salicylates action with the membrane and its effect on outer hair cell electrophysiology. This initial research will lay the groundwork for understanding the effect of amphiphilic drugs, such as salicylate and chlorpromazine, on the properties of biological membranes, and thereby help to elucidate the molecular mechanisms for these amphiphiles effects on the hearing ability. The proposed work will provide results to be compared to the experimental work of our collaborators, Drs. William E. Brownell (Baylor Coll. Med.) and Robert Raphael (Rice Univ.).