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

Hall, Stephen C. L. ; Tognoloni, Cecilia ; Charlton, Jack ; Bragginton, Éilís C. ; Rothnie, Alice J. ; Sridhar, Pooja ; Wheatley, Mark ; Knowles, Timothy J. ; Arnold, Thomas and Edler, Karen J. LU orcid , et al. (2018) In Nanoscale 10(22). p.10609-10619
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... (More)

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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publishing date
type
Contribution to journal
publication status
published
in
Nanoscale
volume
10
issue
22
pages
11 pages
publisher
Royal Society of Chemistry
external identifiers
  • pmid:29845165
  • scopus:85048281822
ISSN
2040-3364
DOI
10.1039/c8nr01322e
language
English
LU publication?
no
additional info
Publisher Copyright: © 2018 The Royal Society of Chemistry.
id
c478501f-ea42-4dba-ab77-25f1da5d3008
date added to LUP
2023-01-18 09:12:25
date last changed
2025-07-27 18:58:59
@article{c478501f-ea42-4dba-ab77-25f1da5d3008,
  abstract     = {{<p>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.</p>}},
  author       = {{Hall, Stephen C. L. and Tognoloni, Cecilia and Charlton, Jack and Bragginton, Éilís C. and Rothnie, Alice J. and Sridhar, Pooja and Wheatley, Mark and Knowles, Timothy J. and Arnold, Thomas and Edler, Karen J. and Dafforn, Tim R.}},
  issn         = {{2040-3364}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{22}},
  pages        = {{10609--10619}},
  publisher    = {{Royal Society of Chemistry}},
  series       = {{Nanoscale}},
  title        = {{An acid-compatible co-polymer for the solubilization of membranes and proteins into lipid bilayer-containing nanoparticles}},
  url          = {{http://dx.doi.org/10.1039/c8nr01322e}},
  doi          = {{10.1039/c8nr01322e}},
  volume       = {{10}},
  year         = {{2018}},
}