Detergent Alternatives: Membrane Protein Purification Using Synthetic Nanodisc Polymers

The development of styrene maleic acid (SMA) and diisobutylene maleic acid (DIBMA) copolymers provides an alternative to traditional detergent extraction of integral membrane proteins. By inserting into the membrane, these polymers can extract membrane proteins along with lipids in the form of native nanodiscs made by poly(styrene co-maleic anhydride) derivatives. Unlike detergent solubilization, where membrane proteins may lose annular lipids necessary for proper folding and stability, native nanodiscs allow for proteins to reside in the natural lipid environment. In addition, polymer-based nanodiscs can be purified using common chromatography methods similar to protocols established with detergent solubilization purification. Here we describe the solubilization screening and purification of an integral membrane protein using several commercial copolymers.