Polymer Nanodiscs and Their Bioanalytical Potential

Abstract

Membrane proteins (MPs) play a pivotal role in cellular function and are therefore predominant pharmaceutical targets. Although detailed understanding of MP structure and mechanistic activity is invaluable for rational drug design, challenges are associated with the purification and study of MPs. This review delves into the historical developments that became the prelude to currently available membrane mimetic technologies before shining a spotlight on polymer nanodiscs. These are soluble nanosized particles capable of encompassing MPs embedded in a phospholipid ring. The expanding range of reported amphipathic polymer nanodisc materials is presented and discussed in terms of their tolerance to different solution conditions and their nanodisc properties. Finally, the analytical scope of polymer nanodiscs is considered in both the demonstration of basic nanodisc parameters as well as in the elucidation of structures, lipidprotein interactions, and the functional mechanisms of reconstituted membrane proteins. The final emphasis is given to the unique benefits and applications demonstrated for native nanodiscs accessed through a detergent free process.

Mechanisms of Formation, Structure, and Dynamics of Lipoprotein Discs Stabilized by Amphiphilic Copolymers: A Comprehensive Review

“…Polymers of the first group are the result of modification of SMAnh mainly by means of nucleophilic addition and ring opening (see Figure 1 A) [ 15 ] at the highly reactive anhydride moiety and are thus termed styrene–maleic anhydride copolymer derivatives (SMADs). Among others, this group includes alkylamine derivatives [ 16 ], ethanolamine, ethylene diamine, and styrene maleimide derivatives [ 17 ], glucosamine, N,N-dimethylethylenediamine [ 18 ], and cysteamine [ 19 ].…”

Cryo-Electron Microscopy Snapshots of Eukaryotic Membrane Proteins in Native Lipid-Bilayer Nanodiscs

“…Polymers such as styrene/maleic acid (SMA) or diisobutylene/maleic acid (DIBMA) are able to extract membrane proteins along with a small patch of their native lipid environment, encapsulating them in lipid-bilayer nanodiscs. These nanodiscs allow for the identification and investigation of membrane proteins in a native-like environment, possibly retaining bound ligands, protein–protein, and protein–lipid interactions, thus allowing a closer-to-native view onto membrane proteins. , Recently, the toolbox of amphiphilic polymers has been expanded, resulting in various new polymers designed to overcome earlier limitations such as low pH stability, tolerance toward divalent metal ions, or poor solubilization efficiency. − Because of its electroneutrality and good solubilization efficiency toward complex lipid compositions, the zwitterionic polymer Sulfo-DIBMA has great potential to be applied to complex membrane environments such as those isolated directly from living cells …”

Tailoring Butyl Methacrylate/Methacrylic Acid Copolymers for the Solubilization of Membrane Proteins: The Influence of Composition and Molecular Weight

“…[21][22][23][24][25][26][27][28] Apart from SMA and SMA-like copolymers, several other types of amphiphilic copolymers for membrane protein isolation were developed. [29] These included diisobutylene/maleic acid copolymers (DIBMA) and their derivatives, [16,[30][31][32][33] alkylamine-modified poly(acrylic acid) (APAA), [34] methacroylcholine chloride/butyl methacrylate copolymers (PMA), [35] acrylic acid/styrene copolymers (AASTY), [14,36] modified inulin, [37,38] methylstilbene/maleic acid copolymers (STMA), [39] and cycloalkylamine-modified poly(acrylic acid) (CyclAPol). [40] In addition, in a very recent comprehensive study, Kopf et al presented a number of SMA derivatives with diverse substitution mainly at the aromatic ring, as well as acrylic acid copolymers with substituted styrenes.…”