Membrane protein nanoparticles: the shape of things to come

Biochem Soc Trans. 2018 Dec 17;46(6):1495-1504. doi: 10.1042/BST20180139. Epub 2018 Nov 21.


The use of styrene-maleic acid (SMA) for the purification of a wide range of membrane proteins (MPs) from both prokaryotic and eukaryotic sources has begun to make an impact in the field of MP biology. This method is growing in popularity as a means to purify and thoroughly investigate the structure and function of MPs and biological membranes. The amphiphilic SMA copolymer can effectively extract MPs directly from a native lipid bilayer to form discs ∼10 nm in diameter. The resulting lipid particles, or styrene-maleic acid lipid particles (SMALPs), contain SMA, protein and membrane lipid. MPs purified in SMALPs are able to retain their native structure and, in many cases, functional activity, and growing evidence suggests that MPs purified using SMA have enhanced thermal stability compared with detergent-purified proteins. The SMALP method is versatile and is compatible with a wide range of cell types across taxonomic domains. It can readily be adapted to replace detergent in many protein purification methods, often with only minor changes made to the existing protocol. Moreover, biophysical analysis and structural determination may now be a possibility for many large, unstable MPs. Here, we review recent advances in the area of SMALP purification and how it is affecting the field of MP biology, critically assess recent progress made with this method, address some of the associated technical challenges which may remain unresolved and discuss opportunities for exploiting SMALPs to expand our understanding of structural and functional properties of MPs.

Keywords: membrane proteins; protein purification; structural biology; structural characterisation.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Maleates / chemistry
  • Membrane Proteins / chemistry*
  • Nanoparticles / chemistry*
  • Polystyrenes / chemistry


  • Maleates
  • Membrane Proteins
  • Polystyrenes
  • styrene-maleic acid polymer