Solid-state NMR methods for studying membrane systems

Abstract

Human life would not exist without biological membranes, which are fascinating lamellar bilayers composed of lipids and proteins. These incredibly thin leaflets are spontaneously formed in aqueous environment by lipids, which are amphiphilic molecules occurring in huge variations with respect to their hydrophilic headgroups and their hydrophobic fatty acid chains. Eukaryotic cells can easily obtain over a thousand different lipid variations. These lipids provide membranes with their basic physicochemical features, essential to exert their biological function in a concerted action with their inherent proteins. To understand the unique features of membranes-from the individual lipid to the cooperative structural and dynamic behavior of the entire leaflet -NMR has provided a wealth of atomic-level insight. In contrast to many other structural biology approaches, NMR can use non-perturbing reporters (naturally or synthetically introduced) to monitor the behavior of the membrane under physio±logical conditions, including elevated temperature, and it can follow the structural and dynamic response of membranes and their constituents upon physiological activities. This way it can elucidate the essential lipid-lipid and lipid-protein interactions that underpin the membrane's function. NMR is ideal as it can exploit the naturally occurring nuclei (31P, 14N, 13C, 1H) within the lipids as well as synthetically incorporated deuterons as non-perturbing reporters of the structure and dynamics within the bilayer. In this manner a wide range of membrane functions have been elucidated, ranging from basic interactions with ions, small drug molecules, but also to peptides and proteins involved in numerous biological events. NMR has also contributed to the study of domain formation in membranes, where nanodomains and rafts have emerged as important factors in the regulation of several important biological processes. Some of the recent exciting developments are summarized in this chapter.