(526a) Nanoparticle Binding Induces Size and Surface-Dependent Restructuring and Aggregation of Liposomes

Physical interactions between nanoparticles and lipid bilayers have direct relevance to, for example, the design of hybrid nanoparticle/liposome assemblies and the potential for nanoparticle-induced biomembrane destabilization, which may contribute to nanoparticle cytotoxicity. Depending on their size and surface chemistry, nanoparticles can induce membrane pore formation, lipid ordering or disordering, and changes in membrane fluidity. Using synthetic lipid bilayers, physical nanoparticle-membrane interactions that underlie these mechanisms can be determined in model systems. In this presentation, we will discuss how anionic and cationic iron oxide nanoparticles (Fe₂O₃ or Fe₃O₄) with diameters ranging from 5 to 50 nm interact with zwitterionic and charged lipid bilayer vesicles or liposomes, and lead to size and surface-dependent lipid phase separation, bilayer permeabilization, and liposome aggregation. These phenomena are examined as a function of the lipid to nanoparticle ratio and the degree of liposome surface coverage by the nanoparticles (0-100%) using differential scanning calorimetry, fluorescence spectroscopy, and cryogenic transmission electron microscopy, respectively. Our results show that, for oppositely charged nanoparticles and liposomes where binding is driven by electrostatic attraction, 5 nm nanoparticles even coat liposome surfaces and reduce lipid melting cooperativity, but do not cause lipid phase separation or liposome aggregation. In contrast, 15 and 50 nm nanoparticle bind randomly and yield phase separation and significant liposome aggregation. Furthermore, 50 nm nanoparticles are able to extract lipids from the bilayers to yield pores in the liposomes and supported lipid bilayers on the nanoparticles. Ultimately, the ability to quantify, mitigate, or exploit nanoparticle-membrane interactions could have broad implications in nanotoxicology and nanomedicine.