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Localization of Cholesterol within Supported Lipid Bilayers Made of a Natural Extract of Tailor-Deuterated Phosphatidylcholine
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Life Sciences Group, Institute Laue-Langevin , 71 Avenue des Martyrs, BP 156, 38042 Grenoble Cedex 9, France.ORCID iD: 0000-0003-3458-887X
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
Department of Pharmacy, Uppsala University , Uppsala 75237, Sweden.
Life Sciences Group, Institute Laue-Langevin , 71 Avenue des Martyrs, BP 156, 38042 Grenoble Cedex 9, France.
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2018 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 34, no 1, p. 472-479Article in journal (Refereed) Published
Abstract [en]

Cholesterol is an essential component of mammalian membranes and is known to induce a series of physicochemical changes in the lipid bilayer. Such changes include the formation of liquid-ordered phases with an increased thickness and a configurational order as compared to liquid-disordered phases. For saturated lipid membranes, cholesterol molecules localize close to the lipid head group-tail interface. However, the presence of polyunsaturated lipids was recently shown to promote relocation of cholesterol toward the inner interface between the two bilayer leaflets. Here, neutron reflection is used to study the location of cholesterol (both non-deuterated and per-deuterated versions are used) within supported lipid bilayers composed of a natural mixture of phosphatidylcholine (PC). The lipids were produced in a genetically modified strain of Escherichia coli and grown under specific deuterated conditions to give an overall neutron scattering length density (which depends on the level of deuteration) of the lipids matching that of D2O. The combination of solvent contrast variation method with specific deuteration shows that cholesterol is located closer to the lipid head group-tail interface in this natural PC extract rather than in the center of the core of the bilayer as seen for very thin or polyunsaturated membranes.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018. Vol. 34, no 1, p. 472-479
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:mau:diva-15232DOI: 10.1021/acs.langmuir.7b02716ISI: 000422611500057PubMedID: 29232134Scopus ID: 2-s2.0-85040308496Local ID: 24231OAI: oai:DiVA.org:mau-15232DiVA, id: diva2:1418753
Available from: 2020-03-30 Created: 2020-03-30 Last updated: 2024-06-18Bibliographically approved
In thesis
1. Model Membranes and Their Interactions with Native and Artificial Lipoproteins
Open this publication in new window or tab >>Model Membranes and Their Interactions with Native and Artificial Lipoproteins
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Atherosclerosis arises from build-up of plaque in the blood, can result in cardiovascular disease and is the largest killer in the west. Low- and high-density lipoproteins are involved in the disease development by depositing and removing lipids to and from artery walls. These processes are complex and not fully understood however, therefore determining the specific roles of the components involved is of fundamental importance in the treatment of the disease.

The work presented in this thesis investigates the production of recombinant tailor-deuterated cholesterol, the structure of cholesterol-containing model membranes and interactions of both native and reconstituted lipoproteins with model membranes. Deuteration is commonly used in neutron scattering for biological samples to provide highly important contrast and the complexity of the native lipoproteins leads to the use of more simple model systems where the compositions can be altered and investigated systematically.

A protocol was developed to produce matchout-deuterated cholesterol for use in neutron scattering studies, as cholesterol is a hugely important component in membranes. The verification of the matchpoint of cholesterol was determined by small-angle neutron scattering and the localisation of cholesterol in model membranes was determined through the use of neutron reflectometry. The interactions of the native and reconstituted lipoproteins with model membranes were also followed by neutron reflectometry, while the structural characterisation of the reconstituted lipoproteins was carried out by small-angle scattering.

Place, publisher, year, edition, pages
Malmö: Malmö universitet, 2020. p. 74
Series
Malmö University Health and Society Dissertations, ISSN 1653-5383 ; 2020:4
Keywords
Model Cell Membranes, Cholesterol, Lipoproteins, Apolipoprotein E, Lipid Exchange, Reconstituted HDL, Atherosclerosis, Deuteration, Neutron Reflectometry, Small-Angle Neutron Scattering
National Category
Physical Chemistry Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:mau:diva-36867 (URN)10.24834/isbn.9789178771325 (DOI)978-91-7877-131-8 (ISBN)978-91-7877-132-5 (ISBN)
Public defence
2020-11-25, Orkanen Hall D138, Nordenskiöldsgatan 10, Malmö, 13:00 (English)
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Supervisors
Available from: 2020-11-18 Created: 2020-11-18 Last updated: 2024-02-23Bibliographically approved

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Publisher's full textPubMedScopushttp://pubs.acs.org/doi/10.1021/acs.langmuir.7b02716

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Waldie, SarahLind, Tania KMaric, SelmaCárdenas, Marité

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