Shedding light on membrane-templated clustering of gold nanoparticles

The use of inorganic nanoparticles in biomedical and biotechnological applications requires a molecular-level understanding of interactions at nano-bio interfaces, such as cell membranes. Several recent reports have shown that gold nanoparticles (AuNP), in the presence of fluid lipid bilayers, aggregate at the lipid/aqueous interface, but the precise origin of this phenomenon is still not fully understood. Here, by challenging synthetic lipid membranes with one of the most typical classes of nanomaterials, citrate-coated AuNP, we addressed the cooperative nature of their interaction at the interface, which leads to AuNP clustering. The ensemble of optical (UV–Vis absorbance), structural (small-angle neutron and X-ray scattering) and surface (X-ray reflectivity, quartz crystal microbalance, atomic force microscopy) results, is consistent with a mechanistic hypothesis, where the citrate-lipid ligand exchange at the interface is the molecular origin of a multiscale cooperative behavior, which ultimately leads to the formation of clusters of AuNP on the bilayer. This mechanism, fully consistent with the data reported so far in the literature for synthetic bilayers, would shed new light on the interaction of engineered nanomaterials with biological membranes. The cooperative nature of ligand exchange at the AuNP-liposome interface, pivotal in determining clustering of AuNP, will have relevant implications for NP use in Nanomedicine, since NP will be internalized in cells as clusters, rather than as primary NP, with dramatic effects on their bioactivity.