Predicting the Nature of the Protein Corona: From Fundamental Modeling to Phenomenological Descriptors

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Abstract#1236053Hall, Carol K.Excitement about the potential of nanotechnology to revolutionize the fields of electronics, materials, medicine, and energy is tempered by concerns about the impact of engineered nanomaterials on the environment and on human health. The small sizes that make nanomaterials so attractive for the creation of new molecular-scale engineering devices render them highly susceptible to adsorption by the human body through inhalation, ingestion and skin penetration. Previous studies suggest that toxicity is related to the physicochemical properties of nanoparticles such as size, shape, surface area, charge, agglomeration status, and hydrophobicity but no general trends have been established. Our research is based on the current thinking that a key step in the body's response to nanoparticle intrusion is the formation of the protein corona, an envelope surrounding the nanoparticle containing proteins adsorbed from the biological fluid following initial exposure. The long term goal of the proposed research is to develop a correlation tool capable of predicting the nature and composition of the protein corona on engineered nanomaterials. This research is intended to be the first step in the development of risk assessment models for nanoparticles. Subsequent steps will be done with collaborators who plan to use the correlation to help predict the in vivo disposition (ADME) of nanomaterials, develop physiologically- based pharmacokinetic (PBPK) models and ultimately create risk assessment model. Intellectual Merit: The objectives are: (1) to predict which proteins in biological fluids adhere to specific engineered nanomaterials, (2) to provide a set of descriptors that characterize the composition and physico-chemical properties of the corona of a given engineered nanomaterial, and (3) to use these tools to rank order the affinities of proteins for specific nanoparticles. Multiscale modeling will be used to determine geometric and energetic parameters for a new intermediate-resolution model, "PRIME/NP" for protein/nanoparticle systems. Energy calculations based on PRIME/NP will be used to predict nanoparticle/protein affinities, and discontinuous molecular dynamics (DMD) simulations will be used to model competitive adsorption of proteins on nanoparticles.Broader Impacts: The proposed research could impact research in the area of biomaterials where the biocompatibility of medical implants is an issue. In addition to training a (female) Ph.D student, research and education will be fostered by: (1) using nanoparticle-protein corona formation, its relation to the potential toxicity of engineered nanomaterials, and the response to this issue by government and society as the basis for examples developed for the PI's undergraduate chemical engineering thermodynamics course, (2) creating a power-point presentation describing the basics of nanotechnology and measurement of toxicity for dissemination via the web, and (3) making a video presentation targeted for general audiences that shows how molecular-level computer simulation can be used to understand nanoparticle toxicity The PI will continue her considerable but informal activities to broaden the opportunities for women and will introduce a brown bag lunch series for women graduate students and postdocs in her department at NCSU.