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Influence of Block Microstructure on the Interaction of Styrene-Maleic Acid Copolymer Aggregates and Lipid Nanodiscs

Neville, George M. ; A. Nasser, Aya ; Doutch, James ; King, Stephen ; Estrela, Pedro ; Whitley, Paul ; Price, Gareth J. and Edler, Karen J. LU orcid (2026) In Soft Matter 22(4). p.994-1007
Abstract
Investigation of the properties of membrane proteins (MPs) is essential
to the successful development of medicines and biotechnology. However,
their study is often complicated by denaturation caused by the use of
detergents during conventional extraction methods. Copolymers of styrene
and maleic acid (SMA) have shown promise in extracting MPs directly
from cells while reconstituting lipid membranes into nanodiscs. Despite
their potential, there remains a dearth of information on the precise
interactions that take place between the copolymers and lipid membranes
although they are known to be sensitive to small variations in copolymer
composition or structure. We have used reversible
... (More)
Investigation of the properties of membrane proteins (MPs) is essential
to the successful development of medicines and biotechnology. However,
their study is often complicated by denaturation caused by the use of
detergents during conventional extraction methods. Copolymers of styrene
and maleic acid (SMA) have shown promise in extracting MPs directly
from cells while reconstituting lipid membranes into nanodiscs. Despite
their potential, there remains a dearth of information on the precise
interactions that take place between the copolymers and lipid membranes
although they are known to be sensitive to small variations in copolymer
composition or structure. We have used reversible
addition–fragmentation chain transfer (RAFT) polymerisation to
synthesise SMA copolymers with equivalent molar mass, but with inverted
block sequences and end group termini. Through a range of experiments,
including dynamic light scattering and small-angle neutron scattering
(SANS) on SMA aggregates and nanodisc formation studies using UV-vis
spectroscopy with both model DMPC lipids and E. coli membranes,
the impact of both block distribution and end group chemistry on
copolymer–membrane interactions was investigated. It was found that
mismatched hydrophilic and hydrophobic end groups on the styrene block
and alternating block, respectively, impeded membrane disruption and
subsequent solubilisation. This highlights not only how the amphiphilic
balance of these blocks is important for efficient nanodisc formation,
but also how end groups influence these and may be optimised towards
extraction of more challenging MPs. The work contributes to a better
understanding of SMA behaviour and offers insight into how these
nanomaterials may be better designed and tailored for specific
applications. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Soft Matter
volume
22
issue
4
pages
994 - 1007
publisher
Royal Society of Chemistry
external identifiers
  • scopus:105028875246
ISSN
1744-6848
DOI
10.1039/D5SM01014D
language
English
LU publication?
yes
id
86e5e103-d5c6-4df5-8b35-2c457f2f4675
date added to LUP
2026-01-10 14:39:09
date last changed
2026-02-19 13:35:59
@article{86e5e103-d5c6-4df5-8b35-2c457f2f4675,
  abstract     = {{Investigation of the properties of membrane proteins (MPs) is essential <br>
to the successful development of medicines and biotechnology. However, <br>
their study is often complicated by denaturation caused by the use of <br>
detergents during conventional extraction methods. Copolymers of styrene<br>
 and maleic acid (SMA) have shown promise in extracting MPs directly <br>
from cells while reconstituting lipid membranes into nanodiscs. Despite <br>
their potential, there remains a dearth of information on the precise <br>
interactions that take place between the copolymers and lipid membranes <br>
although they are known to be sensitive to small variations in copolymer<br>
 composition or structure. We have used reversible <br>
addition–fragmentation chain transfer (RAFT) polymerisation to <br>
synthesise SMA copolymers with equivalent molar mass, but with inverted <br>
block sequences and end group termini. Through a range of experiments, <br>
including dynamic light scattering and small-angle neutron scattering <br>
(SANS) on SMA aggregates and nanodisc formation studies using UV-vis <br>
spectroscopy with both model DMPC lipids and <em>E. coli</em> membranes,<br>
 the impact of both block distribution and end group chemistry on <br>
copolymer–membrane interactions was investigated. It was found that <br>
mismatched hydrophilic and hydrophobic end groups on the styrene block <br>
and alternating block, respectively, impeded membrane disruption and <br>
subsequent solubilisation. This highlights not only how the amphiphilic <br>
balance of these blocks is important for efficient nanodisc formation, <br>
but also how end groups influence these and may be optimised towards <br>
extraction of more challenging MPs. The work contributes to a better <br>
understanding of SMA behaviour and offers insight into how these <br>
nanomaterials may be better designed and tailored for specific <br>
applications.}},
  author       = {{Neville, George M. and A. Nasser, Aya and Doutch, James and King, Stephen and Estrela, Pedro and Whitley, Paul and Price, Gareth J. and Edler, Karen J.}},
  issn         = {{1744-6848}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{994--1007}},
  publisher    = {{Royal Society of Chemistry}},
  series       = {{Soft Matter}},
  title        = {{Influence of Block Microstructure on the Interaction of Styrene-Maleic Acid Copolymer Aggregates and Lipid Nanodiscs}},
  url          = {{http://dx.doi.org/10.1039/D5SM01014D}},
  doi          = {{10.1039/D5SM01014D}},
  volume       = {{22}},
  year         = {{2026}},
}