Micelles, Bicelles, Amphipols, Nanodiscs, Liposomes, or Intact Cells: The Hitchhiker’s Guide to the Study of Membrane Proteins by NMR

The vast majority of biophysical studies of membrane proteins (MPs) at the atomic scale are performed in vitro with preparations as homogeneous as possible, where the protein is isolated in a nonnative environment. MP samples for nuclear magnetic resonance (NMR) spectroscopy are no exception to the rule, in particular because purification helps to clearly detect and unambiguously identify signals from the protein of interest. By native environment, we consider the original membrane(s) where the protein exerts its biological role. It is difficult to place artificial systems on a scale defining how well they mimic native membranes, especially when a functional test is difficult or impossible to set up. Indeed, liposomes or nanometric lipid bilayers still represent artificial environments, and, on the contrary, exotic surfactants like amphipols, which could be thought to be inappropriate given their chemical structures, have proven to keep numerous MPs stable and active in solution. Over the past decades, various membrane mimetics have been developed, chosen on the basis of the compatibility with the technique of investigation used, sometimes at the expense of the functionality of the protein. Paradoxically, after so many efforts to improve membrane substitutes, in-cell NMR has known significant advances during the past few years (Selenko and Wagner 2007; Ito and Selenko 2010), which represents a very attractive potential for future NMR studies of MPs in situ (Renault et al. 2012a, 2012b). Chapter 12 Micelles, Bicelles, Amphipols, Nanodiscs, Liposomes, or Intact Cells: The Hitchhiker’s Guide to the Study of Membrane Proteins by NMR