Nanodisc-Forming Polymers for the Extraction of Membrane Proteins

Membrane proteins are estimated to be encoded by 30% of eukaryotic and prokaryotic genomes and are key drug targets. A key challenge in the study of membrane proteins is their low solubility in aqueous media, which necessitates the use of detergents. Lipid nanodisc-forming polymers, most commonly styrene maleic acid polymers (SMA), have emerged as powerful tools, allowing extraction, storage, and study of membrane proteins. SMA (and other related polymers) have several shortcomings including unwanted UV absorption and instability to certain metal ions, and there is significant chemical space that has not been explored to optimize their function. This perspective introduces lipid nanodisc-forming polymers and their application and leads into emerging new polymers as alternatives to SMALPS. We also include a summary of key functional assays that can be used to accelerate the discovery of new polymers, particularly focused on assays that are simple to conduct in parallel or in high throughput and require minimal specialist infrastructure.