Modeling Small-Angle X-Ray Scattering Data for Low Density Lipoproteins : Insights Into The Fatty Core Phase Packing And Transition

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Modeling Small-Angle X-Ray Scattering Data for Low Density Lipoproteins : Insights Into The Fatty Core Phase Packing And Transition

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Publication Article, peer reviewed scientific
Title Modeling Small-Angle X-Ray Scattering Data for Low Density Lipoproteins : Insights Into The Fatty Core Phase Packing And Transition
Author Maric, Selma ; Lind, Tania Kjellerup ; Lyngsø, Jeppe ; Cárdenas, Marité ; Skov Pedersen, Jan
Research Centre Biofilms - Research Center for Biointerfaces
Date 2017
English abstract
Atherosclerosis and its clinical consequences are the leading cause of death in the western hemisphere. While many studies throughout the last decades have aimed at understanding the disease, the clinical markers in use today still fail to accurately predict the risks. The role of the current main clinical indicator, low density lipoprotein (LDL), in depositing fat to the vessel wall is believed to be the onset of the process. However, many subfractions of the LDL, which differ both in structure and composition, are present in the blood and among different individuals. Understanding the relationship between LDL structure and composition is key to unravel the specific role of various LDL components in the development and/or prevention of atherosclerosis. Here, we describe a model for analyzing small-angle X-ray scattering data for rapid and robust structure determination for the LDL. The model not only gives the overall structure but also the particular internal layering of the fats inside the LDL core. Thus, the melting of the LDL can be followed in situ as a function of temperature for samples extracted from healthy human patients and purified using a double protocol based on ultracentrifugation and size-exclusion chromatography. The model provides information on: (i) the particle-specific melting temperature of the core lipids, (ii) the structural organization of the core fats inside the LDL, (iii) the overall shape of the particle, and (iv) the flexibility and overall conformation of the outer protein/hydrophilic layer at a given temperature as governed by the organization of the core. The advantage of this method over other techniques such as cryo-TEM is the possibility of in situ experiments under near-physiological conditions which can be performed relatively fast (minutes at home source, seconds at synchrotron). This approach now allows the monitoring of structural changes in the LDL upon different stresses from the environment, such as changes in temperature, oxidation, or external agents used or currently in development against atherosclerotic plaque build-up and which are targeting the LDL.
DOI https://doi.org/10.1021/acsnano.6b08089 (link to publisher's fulltext.)
Publisher American Chemical Society
Host/Issue ACS Nano;1
Volume 11
ISSN 1936-0851
Pages 1080-1090
Language eng (iso)
Subject cholesteryl ester packing
low-density lipoprotein
small-angle X-ray scattering
Sciences
Research Subject Categories::INTERDISCIPLINARY RESEARCH AREAS
Handle http://hdl.handle.net/2043/24202 Permalink to this page
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