From polymer chemistry to structural biology: The development of SMA and related amphipathic polymers for membrane protein extraction and solubilisation

• Published in: Chemistry and physics of lipids Vol. 221; pp. 167 - 175
• Main Authors: Bada Juarez, Juan Francisco, Harper, Andrew J., Judge, Peter J., Tonge, Stephen R., Watts, Anthony
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.07.2019
• Subjects: Amphipathic polymers; DIBMA; Discoidal lipid nanoparticles; Drug delivery; Hypercoiling amphipathic polymers; Lipid nanoparticles; Lipodisq; Maleic Anhydrides - chemistry; Membrane protein; Membrane Proteins - chemistry; Membrane Proteins - isolation & purification; Molecular Structure; Nanodiscs; Native nanodiscs; Polymer chemistry; Polymer labelling; Polymers - chemistry; SMA lipid nanoparticles; SMA poylmer; SMALP; Solubility; Structural biology; Styrene - chemistry; Surface-Active Agents - chemistry; Native nanodiscs; ABC; Membrane protein; alt-SMA; Discoidal lipid nanoparticles; SMA-SH; Polymer labelling; Drug delivery; SMA poylmer; Lipodisq; Lipid nanoparticles; DIBMA; HDL; Polymer chemistry; MA; SMAnh; SMA lipid nanoparticles; DMPC; SMALP; DPPC; Nanodiscs; PMA; Hypercoiling amphipathic polymers; SMA; EM; MSP; PEAA; CTC; LCP; Amphipathic polymers; Structural biology
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2019.03.008

•The development of amphiphilic polymers, including SMA, that are able to extract membrane proteins into lipid nanoparticles.•Discussion of the chemical behaviour of hypercoiling amphipathic polymers and their response to changes in pH.•Comparison of different amphipathic polymers used to form discoidal lipid nanoparticles and their tolerance to metal ions.•Recent developments in amphipathic polymer design to expand the applications of lipid nanoparticles for structural biology.•Methods for labelling SMA polymers for fluorescence microscopy and in vivo biodistribution studies. Nanoparticles assembled with poly(styrene-maleic acid) copolymers, identified in the literature as Lipodisq, SMALPs or Native Nanodisc, are routinely used as membrane mimetics to stabilise protein structures in their native conformation. To date, transmembrane proteins of varying complexity (up to 8 beta strands or 48 alpha helices) and of a range of molecular weights (from 27 kDa up to 500 kDa) have been incorporated into this particle system for structural and functional studies. SMA and related amphipathic polymers have become versatile components of the biochemist’s tool kit for the stabilisation, extraction and structural characterization of membrane proteins by techniques including cryo-EM and X-ray crystallography. Lipodisq formation does not require the use of conventional detergents and thus avoids their associated detrimental consequences. Here the development of this technology, from its fundamental concept and design to the diverse range of experimental methodologies to which it can now be applied, will be reviewed.