(216h) Predicting the Nature of the Protein Corona Surrounding Nanoparticles

Our knowledge of the risks of exposure to nanoparticles is essentially in its infancy since the current in vivo and in vitro studies of “nanotoxicology” span only a minute subset of the many different types of nanoparticles being made today. In vivo and in vitro risk assessment studies could be bolstered, however, by the addition of computational (in silico) tools to help pinpoint those nanoparticles that are most likely to pose a risk to the public health. A key step in analyzing the risks posed by nanoparticles is to determine the composition of the corona of plasma proteins adsorbed onto the surface of nanoparticles. The nature of the protein corona is expected to have a marked influence on the fate of nanoparticles in the body.

Our goal is to develop a computational toy model for the formation of a protein corona around a hydrophobic nanoparticle.  Our simulations allow for illustrating and quantifying the protein corona phenomenon at a resolution that is currently difficult to access experimentally, and also provide the capability to examine molecular-level structural changes that may occur after protein adsorption. Preliminary discontinuous molecular dynamics simulations with the coarse-grained force field PRIME20 were used to calculate the adsorption of model small peptides (polyalanine, A₁₆) and model large peptides (polytryptophan, W₁₆) onto a hydrophobic nanoparticle with a radius of 4 nanometers. Systems containing 48 chains of A₁₆ and one hydrophobic nanoparticle were simulated to investigate the degree of adsorption onto the nanoparticle as a function of both time and temperature.  We also examined the effect that adsorption had on the folding behavior of A₁₆, namely whether the native folded α-helical structure was disrupted upon adsorption. Competitive adsorption in mixed systems of A₁₆ and W₁₆ where A₁₆ was in excess of W₁₆ has also been simulated and compared with the theoretical adsorption models proposed by Fang and Szleifer.