Unshackling Membrane Protein Research : New Amphiphilic Copolymers for Extraction of Stable, Active Membrane Proteins

Membrane proteins provide a multitude of functions essential to the life of the cell, and yet extracting them in an active form remains exceptionally challenging. In recent times an amphiphilic polymer, poly(styrene-co-maleic acid) (SMA) has gained significant traction as an effective agent for extracting and stabilising membrane proteins in phospholipid nanodiscs. Unlike conventional methods based on detergents, the method also extracts the lipids surrounding the protein, helping to preserve native activity. Although the original SMA polymer provided a good solution for demonstrating the utility of this approach it is becoming increasingly clear that further development of the polymer is required to fully capitalise on the unique aspects of the method. This project aims to address this by providing a technical resource for the community for generating improved, bespoke polymers matched to end users need allowing them to: 1) Tune the lipid environment within the nano-particle to optimise protein activity by introducing a variety of comonomers, including aromatic, linear aliphatic and branched aliphatic into the established maleic anhydride copolymer 2) Harness functionalised "plug-n-play polymers" that allow researchers to easily modify the polymers for downstream applications These polymers will be tested by the community and delivered through an integrated commercial supply chain.