Plasmonic Nanoparticle-Interfaced Lipid Bilayer Membranes.

Plasmonic nanoparticles are widely exploited in diverse bioapplications ranging from therapeutics to biosensing and biocomputing because of their strong and tunable light-matter interactions, facile and versatile chemical/biological ligand modifications, and biocompatibility. With the rapid growth of nanobiotechnology, understanding dynamic interactions between nanoparticles and biological systems at the molecular or single-particle level is becoming increasingly important for interrogating biological systems with functional nanostructures and for developing nanoparticle-based biosensors and therapeutic agents. Therefore, significant efforts have been devoted to precisely design and create nano-bio interfaces by manipulating the nanoparticles' size, shape, and surface ligand interactions with complex biological systems to maximize their performance and avoid unwanted responses, such as their agglomeration and cytotoxicity. However, investigating physicochemical interactions at the nano-bio interfaces in a quantitative and controllable manner remains challenging, as the interfaces involve highly complex networks between nanoparticles, biomolecules, and cells across multiple scales, each with a myriad of different chemical and biological interactions. A lipid bilayer is a membrane made of two layers of lipid molecules that forms a barrier around cells and plays structural and functional roles in diverse biological processes because they incorporate and present functional molecules (such as membrane proteins) with lateral fluidity. Plasmonic nanoparticles conjugated on lipid membranes provide reliable analytical labels and functional moieties that allow for studying and manipulating interactions between nanoparticles and molecules with single-particle resolution; they also serve as efficient tools for applying optical, mechanical, and thermal stimuli to biological systems, which stem from plasmonic properties. Recently, new opportunities have emerged by interfacing nanoparticle-modified lipid bilayers (NLBs) with complex systems such as molecular circuits and living systems. In this Account, we briefly review how plasmonic properties can be beneficially harnessed on lipid bilayer membranes to investigate the structures and functions of cellular membranes and to develop new platforms for biomedical applications. In particular, we discuss the versatility of supported lipid bilayers (SLBs), which are planar lipid bilayers on hydrophilic substrates, as dynamic biomaterials that provide lateral fluidity and cell membrane-like environments. We then summarize our efforts to create a quantitative analytical platform utilizing nanoparticles as active building blocks and SLBs as integrative substrates. Through this bottom-up approach, various functionalized nanoparticles have been introduced onto lipid bilayers to render nanoparticle-nanoparticle, nanoparticle-lipid bilayer, and biomolecule-lipid bilayer interfaces programmable. Our system provides a new class of tools for studying thermodynamics and kinetics in complex networks of nanostructures and for realizing unique applications in biosensing and biocomputing.