Cascading Effects of Nanoparticle Coatings: Surface Functionalization Dictates the Assemblage of Complexed Proteins and Subsequent Interaction with Model Cell Membranes

Interactions of functionalized nanomaterials with biological membranes are expected to be governed by not only nanoparticle physiochemical properties but also coatings or “coronas” of biomacromolecules acquired after immersion in biological fluids. Here we prepared a library of 4–5 nm gold nanoparticles (AuNPs) coated with either ω-functionalized thiols or polyelectrolyte wrappings to examine the influence of surface functional groups on the assemblage of proteins complexing the nanoparticles and its subsequent impact on attachment to model biological membranes. We find that the initial nanoparticle surface coating has a cascading effect on interactions with model cell membranes by determining the assemblage of complexing proteins, which in turn influences subsequent interaction with model biological membranes. Each type of functionalized AuNP investigated formed complexes with a unique ensemble of serum proteins that depended on the initial surface coating of the nanoparticles. Formation of protein–nanop...