Differences in protein distribution, conformation, and dynamics in hard and soft coronas: dependence on protein and particle electrostatics.

We perform all-atom molecular dynamics simulations of a 9 nm-thick protein layer, which consists of serum albumin (SA) or a mixture of SA and immunoglobulin gamma-1, formed on 10 nm-sized cationic, anionic, and neutral polystyrene particles. More than half of the proteins are densely concentrated within a distance of ∼3 nm from the particle surface, while fewer proteins are broadly distributed in the range of 3-9 nm from the particle. This compares favorably with the experimental observations of a hard corona as the first layer adjacent to the particle and a soft corona as a loose protein-network. The conformation and diffusivity of the proteins vary in different positions of the layer, and are to an extent dependent on the protein and particle electrostatics. These, combined with free energy calculations, show that the protein and particle charges do not significantly modify the strength of protein-particle binding but do influence the distribution of proteins in the layer. In particular, a free protein more strongly binds to the complex of a protein and particle than to either one, showing the synergistic effect of already adsorbed proteins and a particle. This helps explain the experimental observation regarding the formation of a denser protein layer and the stronger protein-protein interaction in the hard corona than the soft corona.