The goal of this research program is to develop a novel proteo-lipid membrane architecture that will allow transmembrane protein receptors to be utilized as bioactive components in electrochemically- and optically-based molecular devices. In the R21 phase of the project, we propose to reconstitute functional ion channels into a synthetic, planar supported lipid bilayer (PSLB) that is polymerized yet elastomeric, stabilizing it to conditions that would destroy a fluid lipid bilayer. A self-assembled, ultra-thin conducting polymer (CP) layer will be used as the interface between the proteo-(poly)lipid membrane and an optically transparent, planar indium-tin oxide (ITO) electrode (which will be implemented as a planar waveguide for optical transduction in future phases of the project). Specific binding of ligands to ion channels reconstituted into the PSLB will modulate the flux of probe ions (e.g., K+) through the channels, which will be detected electrochemically via the CP/ITO transducer. Thus by using a CP film to couple the membrane to an ITO electrode, we will create an integrated sensing platform that bridges the biomembrane/inorganic semiconductor interface.
The Specific Aims focus on step-wise construction of each component of the multilayer architecture. At each stage of development, an array of physical/analytical techniques will be used to assess the influence of different materials and preparation methods on the structural and functional properties of the architecture. The major objective is to establish methods to create PSLBs on self-assembled CP/ITO substrates that are structurally stabilized, maintain the bioactivity of incorporated ion channels, and allow for efficient electrochemical transduction of channel activity. The long-term objective is to create highly stable proteo-lipid materials that can be dried, stored and reused. Successful development and characterization of these materials will open the way for their implementation in several important areas that rely on bioactive presentation of transmembrane receptors, such as bioassays and biosensors, detection of chemical and biological warfare agents, and high-throughput screening of pharmaceutical libraries.
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| Cheng, Zhiliang; Aspinwall, Craig A (2006) Nanometre-sized molecular oxygen sensors prepared from polymer stabilized phospholipid vesicles. Analyst 131:236-43 |
| Subramaniam, Varuni; Alves, Isabel D; Salgado, Gilmar F J et al. (2005) Rhodopsin reconstituted into a planar-supported lipid bilayer retains photoactivity after cross-linking polymerization of lipid monomers. J Am Chem Soc 127:5320-1 |
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