This project represents a part of a broader effort to fully understand the relevant molecular components required for normal cochlear outer hair cell (OHC) function. The application's long-term objective is to fully characterize the mechanical properties of the OHC's plasma membrane that are important towards a further understanding of the performance of this active cell under various conditions. This project specifically focuses on the OHC plasma membrane fluidity, which may be an important contributor to lipid-protein interactions that lead to the cell's active properties, and these phenomena have yet to be explained. The main hypothesis of this project is that a strong coupling exists between the outer hair cell's tension, fluidity, and membrane proteins/motors active and passive properties. The project's main hypothesis will be tested using a combination of computational, theoretical, and experimental approaches intended to further our basic understanding of the OHC plasma membrane's intrinsic properties, specifically the membrane tension and fluidity.
Specific Aim 1 is to develop a cellular-level, computational model to interpret FRAP experiments of anisotropic OHC membrane lipid lateral diffusion.
Specific Aim 2 is to develop theory, based on statistical mechanics, in order to provide a physical basis for the fluidity (diffusion) coefficients described in SA1.
Specific Aim 3 is to experimentally quantify membrane fluidity dependence on membrane tension in a less complex system, and use this to validate the theory in SA2. Relevance: Cochlear outer hair cells (OHCs) are necessary for normal hearing, and the mechanical properties of this cell's plasma membrane are important for the OHC's function. This study uses a combination of techniques to help explain how one of these membrane properties, the membrane fluidity, depends on different natural conditions in the OHC plasma membrane. ? ? ? ?
