This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.There is growing consensus amongst private, industrial, and government agencies that the potential toxicity of synthetic inorganic nanomaterials must be identified early in order to characterize environmental and health risks and reduce public skepticism. Specific questions have arose concerning the uptake, accumulation, transport, and disruptive effects of nanoparticles in biological systems. Given the wide range of nanoparticle compositions, sizes, shapes, and surface functionalities characterizing toxicity has become a daunting task. The objective of this project is to synthesize biomimetic model cell membranes (i.e. multicomponent lipid bilayers) and conduct mechanistic studies on membrane interactions with synthetic nanoparticles. Conventional theories of toxicity and anesthesia have centered on membrane disruption and molecular partitioning. First, membranes composed of zwitterionic lipids, anionic lipids, and cholesterol will be synthesized via liposome preparation techniques and exposed to native and surface functionalized nanoparticles. Of immediate interest are sub-5 nm titania, C60 fullerene, gold, and silver particles. Changes in membrane thermodynamic and transport properties, such as phase behavior, lipid ordering, and diffusivity, reveal mechanistic information on nanoparticle/membrane interactions stemming from van der Waals, electrostatic, hydrophobic, and undulation forces. Fluorescence spectroscopy and differential scanning calorimetry will be used to evaluate these properties. The influence of interaction mechanisms on membrane morphology will be examined by dynamic light scattering and cryogenic transmission electron microscopy an extremely powerful visualization technique. In addition to the toxicological information that is expected to be gained from nanoparticle/cell membrane studies, the interaction mechanisms that are revealed will be used in the future to create new nanoparticle-based therapeutics and hybrid bio/nanomaterials.
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