Membrane proteins make up ~30% of the genome of a typical eukaryotic cell, yet due largely to a strict requirement of a highly mobile, native-like biomembrane microenvironment, these molecules have not been widely built into functional materials. Membrane protein structure is often highly complex, typified by large, multi-subunit complexes that not only span the lipid bilayer but also contain large (>2 nm) cytoplasmic and extracellular domains that protrude from the membrane. Our current studies are focused on the implementation of a biomimetic approach to create solid-supported biomembranes interfaced with micro- and nanostructures.

To functionalize materials with active membrane proteins, the challenge is to build stabilized, supported biomembranes in which the substrate to biomembrane spacing can be controlled to accommodate larger membrane protein systems such as the ABC transporter proteins. In essence, our main objective is to create a biomimetic, surface-tethered artificial cytoskeleton where membrane-bound polymer tethered bioconjugates anchor the lipid bilayer at interfaces. Furthermore, the anchoring of biomembranes in this fashion could lead to assemblies that could hold up to shear, flow, and friction in challenging microenvironments such as found in microdevices, biomaterials, nanoporous membranes, and on micropipette surfaces.

Confocal fluorescence microscopy was utilized to analyze the tether-supported bilayer structures on silica microspheres, micropipettes, and in nanoporous anodic aluminum oxide (AAO) membrane filters with 200 nm and 100 nm pore diameters. We have initiated fluidity studies of the supported membranes using fluorescence recovery after photobleaching (FRAP) in these systems. Scanning and Cryo- electron microscopy has been used in concert with CLSM to characterize the micro or nanostructures formed. These systems have been employed as a new substrate used to functionally immobilize the yeast drug efflux pump PDR5 (as a GFP fusion), a member of the ATP binding cassette (ABC) transporter superfamily. These assemblies are being used to build highly miniaturized in vitro models of multidrug resistance for high-throughput screening and drug discovery. We furthermore aim to develop new functional materials and nanoscale imaging and diagnostic tools based on membrane protein active functions and molecular recognition.