A review of traditional and emerging methods to characterize lipid–protein interactions in biological membranes

Current understanding of the cell membrane suggests that it is a patchwork structure composed of many proteins and lipids that are not all freely diffusing, but rather can take part in dynamic microdomains within the plane of the membrane. These domains can form or be maintained in several ways, such as "lipid shells" around proteins and/or cytoskeletal compartmentalization. Interactions within a micro-environment not only co-localize multiple components of some functional unit, but also may be involved in the regulation of that unit's activity. However, studies of protein-lipid associations and their impacts on protein activity are challenging for a number of reasons. In this review we describe the salient features of classical and emerging methodologies for studying protein-lipid interactions and their limitations.