Membrane Protein-based Nanostructured Materials (pilot)

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Nanostructured materials such as quantum dot nanoparticles have provided rich new palette of functionalities for biosensing and other biomedical applications that exploit their size-dependent properties. Most prominent among these properties are nanoscale quantum confinement effects that have led to a new class of luminescent nanobiosensors of exceptional photostability and brightness. The functionalization of these nanoparticle "beacons" with proteins capable of specific binding interactions for biosensing and diagnostics has thus far been limited to soluble proteins such as monoclonal antibodies and enzymes. At present, arguably the most important class of cellular proteins, namely integral and peripheral membrane proteins, has not yet been interfaced with luminescent nanoparticles. As initiated in this proposed research, construction of this unexplored class of biomembrane-nanoparticle hybrid systems will lead to new sensors, probes and diagnostics based on membrane protein molecular recognition and active function. To functionalize nanostructured materials with active membrane proteins, the first challenge is to position and stabilize intact lipid bilayers onto surfaces with high curvature relative to the biomembrane thickness. Furthermore, an overriding concern is to attempt to closely replicate the lipid composition and membrane fluidity of the receptor's natural microenvironment so that conformational changes or dimerization processes involved in native molecular recognition can occur. Our goal is to build a biomimetic, nanoparticle-tethered artificial cytoskeleton where membrane-spanning protein-polymer bioconjugates provide the strong anchoring needed to build stable lipid bilayers with active membrane proteins onto nanoparticles. With this method we aim to achieve the deposition of intact, stabilized biomembranes onto nanoscopic structures at length scales that have not yet been explored. We envision multiple applications of biomembrane-quantum dot hybrid systems that could impact public health including: 1. New diagnostics and probes based on dimerization of both membrane diffusible ligands and receptors 2. Nanoparticle targeting and imaging probes based on surface membrane proteins, 3. Highly miniaturized drug screening methods, potentially at the single molecule level.