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

Research output: Contribution to journalArticle

  • Stephen C.L. Hall
  • Cecilia Tognoloni
  • Jack Charlton
  • Éilís C. Bragginton
  • Alice J. Rothnie
  • Pooja Sridhar
  • Mark Wheatley
  • Timothy J. Knowles
  • Thomas Arnold
  • Karen J. Edler
  • Tim R. Dafforn
Original languageEnglish
Pages (from-to)10609-10619
Number of pages11
JournalNanoscale
Volume10
Issue number22
Early online date24 May 2018
DOIs
DateAccepted/In press - 23 May 2018
DateE-pub ahead of print - 24 May 2018
DatePublished (current) - 14 Jun 2018

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.

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via the Royal Society of Chemistry at https://doi.org/10.1039/C8NR01322E . Please refer to any applicable terms of use of the publisher.

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