Membrane Solubilization by Styrene-Maleic Acid Copolymers: Importance of Polymer Length and Comonomer Sequence

Styrene-maleic acid (SMA) copolymers are excellent alternatives to detergents for the extraction of membrane proteins from cellular membranes. The copolymers are able to solubilize membranes in the form of native nanodiscs which are stabilized by the copolymer, allowing for the characterization of membrane proteins in their native lipid environment. Commercially available SMA copolymers are polydisperse, having large variations in their length distribution. Using synthetic lipid model systems in conjunction with copolymers having more defined length distributions it has been observed that polymer length is an important parameter in determining both the kinetics of solubilization as well as the properties of the resulting nanodiscs [1]. Here we investigated whether the observed role of polymer length also translates to biological membranes, comprising a rich diversity of lipids as well as proteins. Interestingly, in contrast to synthetic model lipid systems where the smallest polymer is the most efficient solubilizer, biomembranes seem to have an optimum length that is somewhat larger. In addition to polymer length, several other environmental factors were explored. Different sources of biomembranes were tested together with different SMA copolymers having better defined length distributions. The results of these experiments will be shown and the effects will be compared with those of commercially available SMA copolymers. The study sheds light on the process of biomembrane solubilization and helps in determining optimal copolymer properties and conditions. [1] Juan J. Dominguez Pardo et al., Biophysical Journal, 115, 129-138, (2018).