Combining inorganic nanoparticles with lamellar and non-lamellar lipid bilayers: from interaction to design of smart hybrid nanodevices

Lipid bilayers are the structural building blocks of cell membranes and represent fundamental motifs in engineered soft matter. Understanding their interaction with nanomaterials, and in particular with nanoparticles (NPs), is one of the central challenges of nanomedicine and materials science, pursuing a twofold goal: i) to respond to the urgent quest for the mechanistic understanding of nano–bio interactions, which determine NPs cytotoxicity in living organisms; ii) to enable the rational design of smart NPs/lipid nanodevices of biocompatible nature for multiple technological purposes. In this work, we combine inorganic NPs with synthetic lipid bilayers, either in lamellar or non-lamellar arrangement, with two main purposes. Lipid bilayers are primarily employed as simplified and highly controllable models of cell membranes, enabling the identification of key determinants at stake in the interaction of engineered NPs with biological interfaces. Secondly, we exploit the conjugation of NPs with lipid bilayered-systems to develop hybrid nanostructures with technological relevance. The work presented here is organized in three parts. Part I focuses on the physicochemical investigation of the interaction of Turkevich-Frens citrated gold NPs (AuNPs@CT) with synthetic model bilayers of different physicochemical features: our results shed light on the peculiar clustering process of AuNPs@CT observed onto natural membranes, which, although well-known and biologically relevant, has remained largely unaddressed. In addition, we show that these results find application in the development of a new plasmon-based assay, for the determination of the mechanical properties of natural membranes. In Part II, we extend the investigation to curved-bilayered structures, ubiquitous in cells under certain conditions. Employing a library of gold nanoparticles (AuNPs) with different physicochemical features, we directly compare the interaction of AuNPs with model membranes of different symmetry, i.e. from lamellar to cubic architectures, encountered in diseased cells: these results constitute the first attempt to systematically investigate the impact of membrane curvature in the interaction with nanomaterials. Finally, in Part III, we address the interaction of cubic lipid assemblies with Superparamagnetic Iron Oxide NPs (SPIONs), showing that, beside its fundamental interest, it can be exploited for the development of smart nanostructured hybrids with potential application in the biomedical field. In summary, the results presented in this work advance our current understanding of the events occurring at Nano-bio Interfaces and pave the way for the development of new technological devices, exploiting the conjugation of NPs with lipid bilayers.