This proposal was received in response to Nanoscale Science and Engineering initiative, NSF 04-043, category NIRT.
The proposed work involves the design of nanoparticle probes to study the dynamics of "smart" membrane transport and the size change of membrane pores of living bacterial cells in real time. The model system to be used is the efflux pump (MexA-MexB-OprM) in P. aeruginosa because it extrudes a wide range of structurally and functionally unrelated substrates. The primary research goals are to (1) study the dependence of membrane transport kinetics on the size (1-80 nm), shape (sphere, rod, or triangle), surface charge (negative vs. positive), and properties (hydrophobic vs. hydrophilic) of nanoparticles, (2) study the interactions and assembly of efflux pump proteins in real time in response to the presence of synthesized nanoparticles with different sizes, shapes, surface charges, and properties, and (3) study the cytotoxicity and genotoxicity of the synthesized nanoparticles in vitro and in vivo to identify biocompatible and environmentally-friendly nanoparticles for real-time probing of membrane transport in living cells. This is an interdisciplinary research project in the areas of chemistry, material science and engineering, molecular and cellular biology, and protein engineering involving 4 PIs from Old Dominion University and Northwestern University: Xu (ODU, Chemistry and Biochemistry), Elsayed-Ali (ODU, Electrical and Computer Engineering), Osgood (ODU, Biological Sciences), and Van Duyne (Northwestern, Chemistry and Materials Science). An additional PI from CEA in France (Gillet, Protein Engineering) is also involved.
