Biophysical Descriptors of Nanoparticle Protein Coronas

In biological environments, the formation of nanobio molecular interfaces is a common result of the complex, dynamic interactions that occur at the surface of a nanoparticle (NP) or, more generally, at the surface of an engineered nanomaterial. These interactions involve a variety of biomolecules, mainly proteins, forming a nanoparticle-protein corona (NP-PC) molecular structure. Studies of the NP-PC's biophysical properties form a growing area of research. However, understanding, characterizing, and modeling systematically the biophysical properties and molecular interactions related to NP-PCs in biological environments remains a challenge. Understanding these processes should be achieved at a detailed atomic level; however, molecular studies of NP-PC models are difficult. Here, we report the results of atomistic molecular dynamics (MD) conformational studies of several proteins known to participate in the corona composition of NPs entering the human body. Using several MD-refined protein structures in conjunction with molecular docking, we generate and analyze models of homo- and hetero-oligomers occurring within NP-PCs, their surface biophysical properties (e.g., the hydrophobic fraction of the solvent-accessible surface area, SASA_H), and their surface charge distributions. We used atomistic models of small TiO₂ and SiO₂ particles. Our approach unveils (i) scaling relationships between the NP-PC protein composition and the resulting SASA_H values and (ii) a systematic way to characterize the transition from the "hard" (i.e., NP-proximal) to the "soft" (i.e, NP-distal) corona regions. This method of generating atomistic NP-PC models enables the efficient calculation of biophysical descriptors and, thus, could guide future studies of NP-PC biomolecular interactions and their effects (e.g., risk assessment of nanotoxicity) in diverse biological systems.