A Fundamental Study of Nanoparticle–Protein Mutual Interactions:

1. A Fundamental Study of Nanoparticle–Protein Mutual Interactions: Role of Nanoparticle Morphology and Size Funded by the NSF Grant number: #0925232 G. Pyrgiotakis1, I. Chernyshova2, P. Sharma1, A. Singh1, S. Ponnurangam2, B. Moudgil1 andP. Somasundaran2 1University of Florida, 2 Columbia University Center for Particulate & Surfactant Systems (CPaSS) IAB Meeting New York, NY August 20th 2009

2. Industrial Relevance • Nanoparticles used in many different industrial processes • CMP process, catalysis, etc • Wide range of nanoparticle-based products: • Energy (e.g. high capacity batteries) • Optical (e.g. antireflective coatings) • Micro/nano-electronics (e.g. capacitors, displays) • Pharmaceuticals (e.g. drug delivery) • Biomedical (e.g. bioimaging) Disposal and environmental fate? Potential toxicity & Interactions with living cells • Particles in physiological fluids interact initially with the proteins • The adsorbed proteins (soft and hard corona) dictate the fate of the particles and can alter their properties Lynch, I., Dawson, K.A. Protein-nanoparticle interactions, Nano Today, 2008, 3, 40-47.

3. Hypothesis Mutual Interactions: The localized features of the particles can influence the protein adsorption and the adsorption can affect the particle proteins The protein conformation depends on the various particle surface properties. Size, shape, surface charge, roughness and porosity The adsorbed proteins are affecting the particle properties. Dissolution, electronic properties.

4. Objective • Investigate: • The effect of surface properties (size, shape, surface charge, roughness and porosity) on protein adsorption • How the protein adsorption affects the particle properties. • Approach • Spectroscopy & computer simulation technique to understand fundamentals of protein adsorption and conformation of adsorbed proteins. • Research focus – localized features of the surface as opposed to the average measured values. • Simulate the nanoparticle features on a flat surface to measure the localized effects using AFM

5. Proposed Substrate – Protein System 500 nm 100 nm • Hematite Nanoparticles • Major component of cosmetics formulations • Ease of synthesis with wide range of sizes and shapes. • Silica Nanoparticles • Widely used for biomedical applications • Ease of synthesis of different morphology silica particles. Human Serum Albumin • In physiological environments a variety of proteins adsorb on the particles. • Proof-of-concept studies will be conducted with albumin. • Well studied and documented under different conditions.

6. Novelty of the Approach Mesoporous and Nanolithographic surfaces Size Mesoporous Silica 50 nm 50 nm Porosity 2 µm • Porous and non-porous particles. • Simultaneous examination of all the parameters (size and pores). • Use pores to simulate the roughness. • Sol-Gel chemistry allows for variation in the pore size and particle size. • Traditional methods for simulating roughness (ion beam, chemical etching) yield non-uniform features at nanoscale scales. • Nanolithography has better control • of the nanoscale features.

7. Deliverables • Year-End Deliverables • Develop the protocols and optimize the procedures to investigate protein-substrate interactions at localized features level. • Gather proof-of-concept data for a systematic and comprehensive study. • Long Term Deliverables • Derive scaling laws correlating the protein adsorption and the surface features. • Develop methodologies to include other organic molecules such surfactants and more relevant proteins.

8. Timeline Mesoporous Nanolithography AFM, XPS, Zeta Potential AFM for localized features Particle/surface synthesis Size, pores var. Particle Characterization Hematite particles synthesis Hematite particle Character. Quantum chemistry modeling Protein Packing Proteins in solution Proteins on surface Proteins on particles On mesoporous surfaces Raman, FTIR, NMR etc Protein Conform. On silica particles Raman, FTIR, NMR etc On hematite particles Raman, FTIR, NMR etc Est. correlations Acknowledgements: NSF grant #: 0925232 CPaSS, CPaSS members Columbia U. U of Florida