An acid-compatible co-polymer for the solubilization of membranes and proteins into lipid bilayer-containing nanoparticles.

Research output: Contribution to journalArticle

Authors

  • Cecilia Tognoloni
  • Jack Charlton
  • Éilís C Bragginton
  • Alice J Rothnie
  • Pooja Sridhar
  • Thomas Arnold
  • Karen J Edler

Colleges, School and Institutes

External organisations

  • School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. t.r.dafforn@bham.ac.uk.

Abstract

The fundamental importance of membrane proteins in drug discovery has meant that membrane mimetic systems for studying membrane proteins are of increasing interest. One such system has been the amphipathic, negatively charged poly(styrene-co-maleic acid) (SMA) polymer to form "SMA Lipid Particles" (SMALPs) which have been widely adopted to solubilize membrane proteins directly from the cell membrane. However, SMALPs are only soluble under basic conditions and precipitate in the presence of divalent cations required for many downstream applications. Here, we show that the positively charged poly(styrene-co-maleimide) (SMI) forms similar nanoparticles with comparable efficiency to SMA, whilst remaining functional at acidic pH and compatible with high concentrations of divalent cations. We have performed a detailed characterization of the performance of SMI that enables a direct comparison with similar data published for SMA. We also demonstrate that SMI is capable of extracting proteins directly from the cell membrane and can solubilize functional human G-protein coupled receptors (GPCRs) expressed in cultured HEK 293T cells. "SMILPs" thus provide an alternative membrane solubilization method that successfully overcomes some of the limitations of the SMALP method.

Details

Original languageEnglish
Pages (from-to)10609-10619
Number of pages11
JournalNanoscale
Volume10
Issue number22
Early online date24 May 2018
Publication statusPublished - 14 Jun 2018

Keywords

  • HEK293 Cells, Humans, Lipid Bilayers/chemistry, Maleates/chemistry, Nanoparticles/chemistry, Polystyrenes/chemistry, Receptors, G-Protein-Coupled/metabolism, Solubility