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Effect of Cholesterol on the Structure and Composition of Glyco-DIBMA Lipid Particles

[Image: see text] Different amphiphilic co-polymers have been introduced to produce polymer–lipid particles with nanodisc structure composed of an inner lipid bilayer and polymer chains self-assembled as an outer belt. These particles can be used to stabilize membrane proteins in solution and enable...

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Autores principales: Lenz, Julia, Larsen, Andreas Haahr, Keller, Sandro, Luchini, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018766/
https://www.ncbi.nlm.nih.gov/pubmed/36854196
http://dx.doi.org/10.1021/acs.langmuir.2c03019
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author Lenz, Julia
Larsen, Andreas Haahr
Keller, Sandro
Luchini, Alessandra
author_facet Lenz, Julia
Larsen, Andreas Haahr
Keller, Sandro
Luchini, Alessandra
author_sort Lenz, Julia
collection PubMed
description [Image: see text] Different amphiphilic co-polymers have been introduced to produce polymer–lipid particles with nanodisc structure composed of an inner lipid bilayer and polymer chains self-assembled as an outer belt. These particles can be used to stabilize membrane proteins in solution and enable their characterization by means of biophysical methods, including small-angle X-ray scattering (SAXS). Some of these co-polymers have also been used to directly extract membrane proteins together with their associated lipids from native membranes. Styrene/maleic acid and diisobutylene/maleic acid are among the most commonly used co-polymers for producing polymer–lipid particles, named SMALPs and DIBMALPs, respectively. Recently, a new co-polymer, named Glyco-DIBMA, was produced by partial amidation of DIBMA with the amino sugar N-methyl-d-glucosamine. Polymer–lipid particles produced with Glyco-DIBMA, named Glyco-DIBMALPs, exhibit improved structural properties and stability compared to those of SMALPs and DIBMALPs while retaining the capability of directly extracting membrane proteins from native membranes. Here, we characterize the structure and lipid composition of Glyco-DIBMALPs produced with either 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Glyco-DIBMALPs were also prepared with mixtures of either POPC or DMPC and cholesterol at different mole fractions. We estimated the lipid content in the Glyco-DIBMALPs and determined the particle structure and morphology by SAXS. We show that the Glyco-DIBMALPs are nanodisc-like particles whose size and shape depend on the polymer/lipid ratio. This is relevant for designing nanodisc particles with a tunable diameter according to the size of the membrane protein to be incorporated. We also report that the addition of >20 mol % cholesterol strongly perturbed the formation of Glyco-DIBMALPs. Altogether, we describe a detailed characterization of the Glyco-DIBMALPs, which provides relevant inputs for future application of these particles in the biophysical investigation of membrane proteins.
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spelling pubmed-100187662023-03-17 Effect of Cholesterol on the Structure and Composition of Glyco-DIBMA Lipid Particles Lenz, Julia Larsen, Andreas Haahr Keller, Sandro Luchini, Alessandra Langmuir [Image: see text] Different amphiphilic co-polymers have been introduced to produce polymer–lipid particles with nanodisc structure composed of an inner lipid bilayer and polymer chains self-assembled as an outer belt. These particles can be used to stabilize membrane proteins in solution and enable their characterization by means of biophysical methods, including small-angle X-ray scattering (SAXS). Some of these co-polymers have also been used to directly extract membrane proteins together with their associated lipids from native membranes. Styrene/maleic acid and diisobutylene/maleic acid are among the most commonly used co-polymers for producing polymer–lipid particles, named SMALPs and DIBMALPs, respectively. Recently, a new co-polymer, named Glyco-DIBMA, was produced by partial amidation of DIBMA with the amino sugar N-methyl-d-glucosamine. Polymer–lipid particles produced with Glyco-DIBMA, named Glyco-DIBMALPs, exhibit improved structural properties and stability compared to those of SMALPs and DIBMALPs while retaining the capability of directly extracting membrane proteins from native membranes. Here, we characterize the structure and lipid composition of Glyco-DIBMALPs produced with either 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Glyco-DIBMALPs were also prepared with mixtures of either POPC or DMPC and cholesterol at different mole fractions. We estimated the lipid content in the Glyco-DIBMALPs and determined the particle structure and morphology by SAXS. We show that the Glyco-DIBMALPs are nanodisc-like particles whose size and shape depend on the polymer/lipid ratio. This is relevant for designing nanodisc particles with a tunable diameter according to the size of the membrane protein to be incorporated. We also report that the addition of >20 mol % cholesterol strongly perturbed the formation of Glyco-DIBMALPs. Altogether, we describe a detailed characterization of the Glyco-DIBMALPs, which provides relevant inputs for future application of these particles in the biophysical investigation of membrane proteins. American Chemical Society 2023-02-28 /pmc/articles/PMC10018766/ /pubmed/36854196 http://dx.doi.org/10.1021/acs.langmuir.2c03019 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Lenz, Julia
Larsen, Andreas Haahr
Keller, Sandro
Luchini, Alessandra
Effect of Cholesterol on the Structure and Composition of Glyco-DIBMA Lipid Particles
title Effect of Cholesterol on the Structure and Composition of Glyco-DIBMA Lipid Particles
title_full Effect of Cholesterol on the Structure and Composition of Glyco-DIBMA Lipid Particles
title_fullStr Effect of Cholesterol on the Structure and Composition of Glyco-DIBMA Lipid Particles
title_full_unstemmed Effect of Cholesterol on the Structure and Composition of Glyco-DIBMA Lipid Particles
title_short Effect of Cholesterol on the Structure and Composition of Glyco-DIBMA Lipid Particles
title_sort effect of cholesterol on the structure and composition of glyco-dibma lipid particles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018766/
https://www.ncbi.nlm.nih.gov/pubmed/36854196
http://dx.doi.org/10.1021/acs.langmuir.2c03019
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