pH Tunable and Divalent Metal Ion Tolerant Polymer Lipid Nanodiscs

The development and applications of detergent-free membrane mimetics have been the focus for the high-resolution structural and functional studies on membrane proteins. The introduction of lipid nanodiscs has attracted new attention toward the structural biology of membrane proteins and also enabled biomedical applications. Lipid nanodiscs provide a native lipid bilayer environment similar to the cell membrane surrounded by a belt made up of proteins or peptides. Recent studies have shown that the hydrolyzed form of styrene maleic anhydride copolymer (SMA) has the ability to form lipid nanodiscs and has several advantages over protein or peptide based nanodiscs. SMA polymer lipid nanodiscs have become very important for structural biology and nanobiotechnological applications. However, applications of the presently available polymer nanodiscs are limited by their instability toward divalent metal ions and acidic conditions. To overcome the limitations of SMA nanodiscs and to broaden the potential applications of polymer nanodiscs, the present study investigates the tunability of SMA polymer nanodiscs by systematically modifying the maleic acid functional group. The two newly developed polymers and subsequent lipid nanodiscs were characterized using solid-state NMR, FT-IR, TEM, and DLS experiments. The pH dependence and metal ion stability of these nanodiscs were studied using static light scattering and FTIR. The reported polymer nanodiscs exhibit unique pH dependent stability based on the modified functional group and show a high tolerance toward divalent metal ions. We also show these tunable nanodiscs can be used to encapsulate and stabilize a polyphenolic natural product curcumin.