Purification of membrane proteins free from conventional detergents: SMA, new polymers, new opportunities and new insights

Membrane proteins remain a somewhat enigmatic group of biomolecules. On the one hand they mediate some of the most important processes in biology with molecular mechanisms that are often elegantly complex. On the other hand they are exceptionally challenging to produce, making studies of membrane protein structure and function among the most difficult projects undertaken by biochemists. The central issue with studies of a membrane protein has been the need to extract them from their native lipid environment before purification and production of a homogenous sample. Historical approaches have utilized detergent solubilisation but these often lead to a sample with low activity and stability. In the past 15 years a new approach that focuses on preserving the local lipid environment surrounding the membrane proteins has been developed. The latest, and perhaps most complete, incarnation of this method has been the use of polymers based on styrene maleic acid (SMA) to stabilise nanoscale discs of lipid that contain membrane proteins. In this review we examine the range of SMA-related polymers that have now been shown to have utility in the production of membrane proteins. We discuss the differences between the polymers and attempt to discover rules and trends that explain their behavior.