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Membranes 2015, 5(4), 664-684; doi:10.3390/membranes5040664

Effect of Cholesterol on the Structure of a Five-Component Mitochondria-Like Phospholipid Membrane

1
Department of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1, Canada
2
Canadian Neutron Beam Centre, National Research Council, Chalk River, ON K0J 1J0, Canada
3
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada
*
Authors to whom correspondence should be addressed.
Academic Editor: Shiro Suetsugu
Received: 5 August 2015 / Accepted: 16 October 2015 / Published: 30 October 2015
(This article belongs to the Special Issue Membrane Structure and Dynamics)
View Full-Text   |   Download PDF [2590 KB, uploaded 2 November 2015]   |  

Abstract

Cellular membranes have a complex phospholipid composition that varies greatly depending on the organism, cell type and function. In spite of this complexity, most structural data available for phospholipid bilayers concern model systems containing only one or two different phospholipids. Here, we examine the effect of cholesterol on the structure of a complex membrane reflecting the lipid composition of mitochondrial membranes, with five different types of headgroups (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS) and cardiolipin (CL)) and a variety of hydrocarbon tails. This particular system was chosen because elevated cholesterol contents in mitochondrial membranes have been linked to a breaking down of Bax-mediated membrane permeabilization and resistance to cancer treatments. High resolution electron density profiles were determined by X-ray reflectivity, while the area per phospholipid chain, Apc, and the chain order parameter, SX-ray, were determined by wide-angle X-ray scattering (WAXS). We show that chain order increases upon the addition of cholesterol, resulting in both a thickening of the lipid bilayer and a reduction in the average surface area per phospholipid chain. This effect, well known as cholesterol’s condensation effect, is similar, but not as pronounced as for single-component phospholipid membranes. We conclude by discussing the relevance of these findings for the insertion of the pro-apoptotic protein Bax in mitochondrial membranes with elevated cholesterol content. View Full-Text
Keywords: phospholipid; cholesterol; mitochondria; cardiolipin; apoptosis; Bax; X-ray diffraction; reflectivity; wide angle X-ray scattering phospholipid; cholesterol; mitochondria; cardiolipin; apoptosis; Bax; X-ray diffraction; reflectivity; wide angle X-ray scattering
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Cathcart, K.; Patel, A.; Dies, H.; Rheinstädter, M.C.; Fradin, C. Effect of Cholesterol on the Structure of a Five-Component Mitochondria-Like Phospholipid Membrane. Membranes 2015, 5, 664-684.

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