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For nanoparticles that have been released into the environment, the cell membrane represents an initial site of interaction with eukaryotic cells. The encounter of nanoparticles with cellular membranes may alter membrane structure and function, lead to uptake into cells, or elicit adverse biological responses. Supported lipid bilayers have proven to be valuable ex vivo models for biological membranes, allowing investigation of their mechanisms of interaction with nanoparticles with a degree of control impossible in living cells. To date, the majority of research on nanoparticle interaction with supported lipid bilayers has employed membranes composed of single or binary mixtures of phospholipids. Cellular membranes contain a wide variety of lipids and exhibit lateral organization. Ordered membrane domains enriched in specific membrane components, also referred to as lipid rafts, have not been explored with respect to their interaction with nanoparticles. Here we develop model membranes containing segregated domains differing in fluidity that are amenable to investigation by a variety of surface-sensitive analytical techniques and demonstrate that these domains influence the extent of nanoparticle attachment to model membranes. We determined conditions that allow reliable formation of bilayers containing liquid-ordered domains enriched in sphingomyelin and cholesterol and confirmed their morphology by structured illumination and atomic force microscopies. We demonstrate that the presence of liquid-ordered domains increases attachment of cationic gold nanoparticles to model membranes relative to those lacking such domains under near physiological ionic strength conditions (0.1 M NaCl) at pH 7.4. We anticipate that these results will serve as the foundation for and motivate further study of nanoparticle interaction with phase-segregated domains.

Formation of supported lipid bilayers containing phase-segregated domains and their interaction with gold nanoparticles