Mesoscopic simulations of protein corona formation on zwitterionic peptide-grafted gold nanoparticles

Understanding protein corona formation on nanoparticle surface is crucial to broad applications of nanomedicine and nanotechnologies. In this work, we performed mesoscopic coarse-grained molecular dynamics simulations to study the effect of nanoparticle surface’s charge distribution on protein corona formation. Short peptide chains consisting of alternating oppositely charged amino acid residues were grafted on a gold nanoparticle surface to generate surface zwitterionic charge distribution and the ovispirin-1 peptide of high positive charge density was adopted as a model system to examine the zwitterionic nanoparticle’s antibiofouling activities. Our mesoscopic simulations showed that the mixing of opposite charges on the nanoparticle’s surface can significantly reduce the nanoparticle’s electrostatic interactions with ovispirin-1 peptides in water. The formation of protein corona on the gold nanoparticle surface is effectively slowed down by 27% compared to a bare gold nanoparticle, thanks to the grafted zwitterionic peptide chains that introduce enhanced interfacial hydration, reduce hydrophobic interactions between the gold nanoparticle’s core and ovispirin-1 peptides, and minimize electrostatic interactions. However, the presence of the small double charge layers as a result of the slightly selective adsorption of different amino acid residues, the local heterogeneity of charge distribution on the nanoparticle surface, and the nanoparticle-ovispirin-1 peptides hydrophobic interactions still result in a monolayer adsorption of ovispirin-1 peptides. Compared to a bare gold nanoparticle, ovispirin-1 peptides are more tilted on the zwitterionic nanoparticle surface.