ABSTRACT
Membrane proteins constitute roughly one-third of all gene products (Tatulian 2003) and play a key role in cell adhesion, recognition, motility, energy production, transport of nutrients, and cholesterol. Nevertheless, the knowledge of the structure-function relationship for membrane proteins is still very limited, and lags behind that of soluble proteins (Popot and Engelman 2000, White and Wimley 1999, White et al. 2001). The handling of membrane proteins requires a lipid environment that closely matches the conditions in the living cell. Many questions pertaining to membrane processes or conformational changes of a membrane-based protein, due to an external perturbation, can be addressed by solid-supported or tethered lipid bilayers (Naumann et al. 2003a, Schiller et al. 2003). These are novel model membrane platforms that allow for a simultaneous characterization of the structural and the functional aspects of membrane processes and the evaluation of the correlation between both (Knoll et al. 2004). Planar lipid bilayers on solid supports appear as promising alternative to liposomes, which are not amiable for the application of surface analytical techniques to investigate proteins in a functionally active form. However, developments were originally directed more toward understanding lipid bilayers rather than incorporating proteins (Schonherr et al. 2004). The obvious drawback of lipid bilayers, directly coating planar surfaces, is that membrane proteins often have domains that extend into the aqueous phase and consequently require to be displaced from the solid surface by a certain distance in order to avoid destructive interactions which may occur upon contact with the solid phase. Moreover, active proteins are often involved in the transport of ions, water, and small molecules. Hence, an aqueous submembrane reservoir is also necessary to accommodate these entities (Tanaka and Sackmann 2005). In order to solve these problems, linker or tether molecules were developed, which are attached on the one side to the proximal leaet of the lipid bilayer and on the other side provide functional groups for attaching a linker molecule to the surface. On gold surfaces this can be, for example, a sulfur functionality group. These so-called thiolipids self-assemble on the solid surface into a monolayer, which upon fusion with liposomes form a tethered lipid bilayer (tBLM) (Terrettaz et al. 2003). A tBLM schematic is shown in Figure 18.1.
