Tunable Terpolymer Series for the Systematic Investigation of Membrane Proteins

Membrane proteins (MPs) are critical to cellular processes and serve as essential therapeutic targets. However, their isolation and characterization are often impeded by traditional detergent-based methods, which can compromise their native states, and retention of their native lipid environment. Amphiphilic polymers have emerged as effective alternatives, enabling the formation of nanoscale discs that preserve MPs' structural and functional integrity. We introduce a novel series of poly(styrene-<i>co</i>-maleic acid-<i>co</i>-(<i>N</i>-benzyl)maleimide) (BzAM) terpolymers with tunable amphiphilicity, synthesized through controlled polymerization. Designed to mimic and improve upon industry-standard poly(styrene-<i>co</i>-maleic acid), these well-defined terpolymers offer enhanced control over molecular weight and distribution, allowing for systematic evaluation of polymer properties and their effect on membrane solubilization. The BzAM series effectively solubilized membranes and demonstrated a direct correlation between polymer hydrophobicity and solubilization efficiency of bacterial ABC transporter, Sav1866. This research highlights the importance of rational polymer design in MP research and provides a foundation for future developments.