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

DOI: 10.1039/C8NR01322E DOI Help

Authors: Stephen C. L. Hall (University of Birmingham; Diamond Light Source) , Cecilia Tognoloni (University of Bath) , Jack Charlton (University of Brimingham) , Eilis C. Bragginton (University of Bristol) , Alice J. Rothnie (Aston University) , Pooja Sridhar (University of Brimingham) , Mark Wheatley (University of Brimingham) , Timothy J. Knowles (University of Birmingham) , Thomas Arnold (Diamond Light Source; University of Bath; European Spallation Source ERIC) , Karen J. Edler (University of Bath) , Tim R. Dafforn (University of Birmingham)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nanoscale

State: Published (Approved)
Published: May 2018
Diamond Proposal Number(s): 9727

Open Access Open Access

Abstract: The fundamental importance of membrane proteins in drug discovery has meant that membrane mimetic systems for studying membrane proteins is 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.

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: B21-High Throughput SAXS