Effect of PEGylation on the Adsorption and Binding Strength of Plasma Proteins to Nanoparticle Surfaces

The adsorption of plasma proteins (human serum albumin, immunoglobulin γ-1, apolipoproteins A-I and E-III) onto polystyrene surfaces grafted with polyethylene glycol (PEG) at different grafting densities is simulated using an all-atom PEG model validated by comparing the conformations of isolated PEG chains with previous simulation and theoretical values. At high PEG density, the grafted PEG chains extend like brushes, while at low density, they significantly adsorb to the surface due to electrostatic attraction between polystyrene amines and PEG oxygens, forming a PEG layer much thinner than its Flory radius. Free energy calculations show that PEGylation can either increase or decrease the binding strength between proteins and surfaces, to an extent dependent on PEG density and specific proteins involved, in agreement with experiments. In particular, grafted PEG chains not only sterically block the binding between proteins and surfaces but also strongly interact with proteins via hydrogen bonds and electrostatic and hydrophobic interactions, with apolipoproteins exhibiting stronger hydrophobic interactions with PEG than other proteins, implying that these specific protein-PEG interactions help certain proteins remain on the PEGylated surface. These simulation findings help explain experimental observations regarding the abundance of specific plasma proteins adsorbed onto nanoparticles grafted with PEG at different densities.