Gold Nanoparticle Adsorption and Uptake are Directed by Particle Capping Agent.

Nanomaterials are revolutionizing the development of novel therapies, with applications ranging from drug delivery and diagnostics to controlling specific biological processes. However, the specific interactions that govern nanomaterial behavior in biological systems remain difficult to elucidate due to the complex dynamic nature of the lipid bilayer environment. Here, a combination of atomic force microscopy and molecular dynamics simulations is used to discover the precise mechanisms by which various ligand-capped 5 nm gold nanoparticles (AuNPs) interact with supported lipid bilayers of pure fluid phospholipids (1,2-di(9Z-octadecenoyl)-sn-glycero-3-phosphocholine (DOPC)). When the ligand capping agent is altered, differences in adsorption and bilayer disruption as a function of capping agent size and charge are observed. Weakly physiosorbed ligands enable the absorption of the AuNP into the bilayer's hydrophobic core, whereas more strongly adsorbed ligands inhibit the complete insertion of the AuNP. However, ligand-dependent headgroup interactions can lead to interfacial adhesion or inhibition of adsorption. These results reveal that the interaction of AuNPs with biological membranes varies depending on the specific capping agent. Notably, the mechanisms may involve cooperative (or synergistic) effects with membrane components, highlighting the importance of understanding these interactions at molecular resolution.