A Fundamental Study of Nanoparticle–Protein Mutual Interactions:

Role of Nanoparticle Morphology and SizeFunded by the NSF Grant number: #0925232

G. Pyrgiotakis1, I. Chernyshova2, P. Sharma1, A. Singh1, S. Ponnurangam2, B. Moudgil1 and P. Somasundaran2

Center for Particulate & Surfactant Systems (CPaSS)IAB Meeting New York, NY

August 20th 2009

1University of Florida, 2 Columbia University

Industrial Relevance

• 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)

Lynch, I., Dawson, K.A. Protein-nanoparticle interactions, Nano Today, 2008, 3, 40-47.

• 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

Disposal and environmental fate?Potential toxicity & Interactions with living cells

• Nanoparticles used in many different industrial processes CMP process, catalysis, etc

Mutual Interactions:The localized featuresof the particles can

influence the protein adsorption and

the adsorption can affectthe particle proteins

1. The protein conformation depends on the various particle surface properties.

Size, shape, surface charge, roughness and porosity2. The adsorbed proteins are affecting the particle properties.

Dissolution, electronic properties.

Hypothesis

Objective

Investigate:1. The effect of surface properties (size, shape, surface charge,

roughness and porosity) on protein adsorption2. 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

Proposed Substrate – Protein System

100 nm500 nm

Silica Nanoparticles• Widely used for biomedical

applications• Ease of synthesis of different

morphology silica particles.

Hematite Nanoparticles• Major component of

cosmetics formulations• Ease of synthesis with wide

range of sizes and shapes.

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.

50 nm50 nm

Novelty of the Approach

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.

Mesoporous SilicaMesoporous and

Nanolithographic surfaces

Porosity

Size

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.

Timeline

Q1 Q2 Q3 Q4

QCM

Mesoporous Nanolithography

AFM, XPS, Zeta PotentialAFM for localized features

Size, pores var. Particle Characterization

Hematite particles synthesisHematite particle Character.

Quantum chemistry modeling

Proteins in solutionProteins on surface

Proteins on particlesOn mesoporous surfaces Raman, FTIR, NMR etc

Par

ticl

e/su

rfac

e sy

nthe

sis

Protein Packing

Pro

tein

C

onfo

rm.

On silica particles Raman, FTIR, NMR etcOn hematite particles Raman, FTIR, NMR etc

Est. correlations

Acknowledgements:NSF grant #: 0925232

CPaSS, CPaSS members

Columbia U.U of Florida