Gold Nanoparticles interacting with Synthetic Lipid Rafts: an AFM investigation

Abstract

Inorganic nanoparticles (NPs) represent promising examples of engineered nanomaterials, providing interesting biomedical solutions in several fields, like therapeutics and diagnostics. Despite the extensive number of investigations motivated by their remarkable potential for nanomedicinal applications, the interactions of NPs with biological interfaces are still poorly understood. The effect of NPs on living organisms is mediated by biological barriers, such as the cell plasma membrane, whose lateral heterogeneity is thought to play a prominent role in NPs adsorption and uptake pathways. In particular, biological membranes feature the presence of rafts, i.e. segregated lipid micro and/or nano-domains in the so-called liquid ordered phase (Lo), immiscible with the surrounding liquid disordered phase (Ld). Rafts are involved in various biological functions and act as sites for the selective adsorption of materials on the membrane. Indeed, the thickness mismatch present along their boundaries generates energetically favorable conditions for the adsorption of NPs. Despite its clear implications in NPs internalization processes and cytotoxicity, a direct proof of the selective adsorption of NPs along the rafts boundaries is still missing to date. Here we use multicomponent Supported Lipid Bilayers (SLBs) as reliable synthetic models, reproducing the nanometric lateral heterogeneity of cell membranes. After being characterized by Atomic Force Microscopy (AFM) and Neutron Reflectivity (NR), multi-domain SLBs are challenged by prototypical inorganic nanoparticles, i.e. citrated gold nanoparticles (AuNPs), under simplified and highly controlled conditions. By exploiting AFM, we demonstrate that AuNPs preferentially target lipid phase boundaries as adsorption sites. The herein reported study consolidates and extends the fundamental knowledge on NPs-membrane interactions, which constitute a key aspect to consider when designing NPs-related biomedical applications.