ABSTRACT
Abbreviations .................................................................................................... 622 References ......................................................................................................... 623
The study the membrane proteins within specialized membrane microdomains, such as lipids enriched in sphingolipids, glycerophospholipids, and cholesterol [1-3] presents some speci c problems. These domains, also called surfactantresistant membranes (DRMs), have been shown to play key roles in cell signaling and protein sorting. Historically, DRMs have been detected by their resistance to solubilization by cold Triton X-100. However, it has been shown that the characteristics of these DRMs are dependant upon the surfactants used in their isolation. For example, Schuck et al. showed that the amounts and types of proteins and lipids associated with DRMs varied dramatically when different surfactants were used to isolate the membrane domain [1]. Another important aspect in membrane protein research is that the surfactant used must be able to maintain a target membrane in a soluble, native and functional form in the absence of the membrane. A surfactant-solubilized state is usually required for protein puri cation, since biological membranes must be disrupted with surfactants to separate individual proteins. Furthermore, many biochemical and biophysical techniques, require solubilized and monodisperse protein. To minimize the potential problems of protein denaturation and aggregation, one of the central issues is to nd conditions where the physical environment of the protein was minimally perturbed despite the dissolution of the original membrane. In fact, most membrane proteins can be readily maintained in a functional, active form while in their native membranes, but may be highly prone to loss of function and aggregation in the surfactantsolubilized state. Thus, a surfactant that is able to closely mimic the physical properties of the original bilayer will be better suited at maintaining the structural integrity of a membrane protein following its extraction from its natural lipidic environment. Indeed, speci c lipids are sometimes required to maintain the structural stability of membrane proteins. Conversely, a “harsh” surfactant that cannot act as an effective membrane substitute is unlikely to maintain protein function.
