Solubilization of Lipid Membranes by Styrene-Maleic Acid Copolymers: Importance of Polymer Composition and PH

Abstract

The styrene-maleic acid (SMA) copolymer is rapidly gaining attention as tool in membrane research due to its ability to directly solubilize lipid membranes into nanodisc particles without the requirement of conventional detergents. Although many different variants of SMA are commercially available, so far mainly those with a styrene-to-maleic acid monomer ratio of 2:1 or 3:1 have been used for model membrane studies as well as for membrane protein extraction.Here, we present a systematic investigation of the effect of SMA composition on its solution properties as well as on its interaction with membranes. A particular focus was the effect of pH, which strongly affects the charge density of the polymer. Using model membranes of di-14:0 PC lipids, we found that membrane solubilization is promoted by a low charge density and by a relatively high fraction of maleic acid units in the polymer.In addition, we used calorimetry and fluorescence methods to investigate the influence of SMA composition on the properties of lipids in nanodisc particles formed of different saturated PCs. We found that all polymers affect the gel-to-liquid crystalline phase transition of the lipids but that the degree of their influence depends on the styrene-to-maleic acid ratio.Altogether, the results show large differences in behavior between different SMA variants, with the one having a styrene-to-maleic acid ratio of 2:1 showing both the highest efficiency in membrane solubilization and the best preservation of lipid bilayer properties in nanodisc particles.