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Book ChapterDOI

X-ray and Neutron Scattering Studies of Lipid–Sterol Model Membranes

TL;DR: A brief review of X-ray and neutron scattering studies of model membranes containing cholesterol and other sterols, highlighting the detailed structural information they provide.
Abstract: Sterols are major components of many biomembranes and are known to play an important role in several biological processes. In order to understand the complex lipid–sterol interactions and their influence on membrane structure and properties, model membranes containing cholesterol and other sterols have been widely studied using a variety of experimental techniques. This chapter gives a brief review of X-ray and neutron scattering studies of these systems, highlighting the detailed structural information they provide.
Citations
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Journal ArticleDOI
TL;DR: The addition of DPPG((-)) to a binary mixture of DPPC/cholesterol induces phase separation between DPPG-rich and cholesterol-rich phases, which indicates that cholesterol localization depends strongly on the electric charge on the hydrophilic head group rather than on the ordering of the hydrocarbon tails.
Abstract: Phase separation in lipid bilayers that include negatively charged lipids is examined experimentally. We observed phase-separated structures and determined the membrane miscibility temperatures in several binary and ternary lipid mixtures of unsaturated neutral lipid, dioleoylphosphatidylcholine (DOPC), saturated neutral lipid, dipalmitoylphosphatidylcholine (DPPC), unsaturated charged lipid, dioleoylphosphatidylglycerol (DOPG((-))), saturated charged lipid, dipalmitoylphosphatidylglycerol (DPPG((-))), and cholesterol. In binary mixtures of saturated and unsaturated charged lipids, the combination of the charged head with the saturation of the hydrocarbon tail is a dominant factor in the stability of membrane phase separation. DPPG((-)) enhances phase separation, while DOPG((-)) suppresses it. Furthermore, the addition of DPPG((-)) to a binary mixture of DPPC/cholesterol induces phase separation between DPPG((-))-rich and cholesterol-rich phases. This indicates that cholesterol localization depends strongly on the electric charge on the hydrophilic head group rather than on the ordering of the hydrocarbon tails. Finally, when DPPG((-)) was added to a neutral ternary system of DOPC/DPPC/cholesterol (a conventional model of membrane rafts), a three-phase coexistence was produced. We conclude by discussing some qualitative features of the phase behaviour in charged membranes using a free energy approach.

65 citations

Journal ArticleDOI
TL;DR: The structure, formation, and biological functions of oxysterols, and previous work on the effect of these molecules on the structure and phase behavior of lipid membranes are described, and results of X-ray diffraction experiments on aligned multilayers of dipalmitoylphosphatidylcholine (DPPC) membranes containing ring-substituted oxysterol are presented.
Abstract: Oxysterols are oxygenated derivatives of cholesterol that form a class of potent regulatory molecules with diverse biological activity. Given the implications of oxysterols in several physiological/pathophysiological pathways of human diseases, it is important to identify how their presence affects the biophysical properties of cell membranes. In this article we first describe the structure, formation, and biological functions of oxysterols, and previous work on the effect of these molecules on the structure and phase behavior of lipid membranes. We then present results of our X-ray diffraction experiments on aligned multilayers of dipalmitoylphosphatidylcholine (DPPC) membranes containing ring-substituted oxysterols. The effect of these molecules on the phase behavior of DPPC membranes is found to be very similar to that of cholesterol. All the oxysterols studied induce a modulated phase in DPPC membranes, similar to that reported in DPPC–cholesterol membranes. However, some differences are observed in the ability of these molecules to suppress the main transition of the lipid and to induce chain ordering, which might be related to differences in their orientation in the bilayer.

10 citations


Cites background from "X-ray and Neutron Scattering Studie..."

  • ...Studies of lipid–cholesterol membranes have shown that this phase occurs only in mixtures with lipids that have a gel phase with non-zero chain tilt (Sarangi et al. 2010)....

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  • ...On the basis of such arguments and the election density map, a structure has been proposed for the Pb phase (Sarangi et al. 2010)....

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References
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Journal ArticleDOI
05 Jun 1997-Nature
TL;DR: A new aspect of cell membrane structure is presented, based on the dynamic clustering of sphingolipids and cholesterol to form rafts that move within the fluid bilayer that function as platforms for the attachment of proteins when membranes are moved around inside the cell and during signal transduction.
Abstract: A new aspect of cell membrane structure is presented, based on the dynamic clustering of sphingolipids and cholesterol to form rafts that move within the fluid bilayer. It is proposed that these rafts function as platforms for the attachment of proteins when membranes are moved around inside the cell and during signal transduction.

9,436 citations


"X-ray and Neutron Scattering Studie..." refers background in this paper

  • ...In recent years, there has been renewed interest in lipid–sterol systems in light of the raft hypothesis [6]....

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  • ...Cholesterol is also believed to be responsible for organizing membrane lipids into submicrometer-sized domains, commonly referred to as rafts [6]....

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Journal ArticleDOI
TL;DR: The uncertainty in structural results for lipid bilayers is being reduced and best current values are provided for bilayers of five lipids.

2,497 citations


"X-ray and Neutron Scattering Studie..." refers background in this paper

  • ...Several important structural parameters, such as the membrane thickness and number of water molecules per lipid, can be estimated once r(z) is known [13,15]....

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  • ...The Lorentz corrected scattered intensity from a stack of bilayers is given by [13],...

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Journal ArticleDOI
TL;DR: This work will review the evidence that rafts exist in cells and focus on their structure, or the organization of raft lipids and proteins, and the role of rafts in signaling in hematopoietic cells.

2,312 citations

Journal ArticleDOI
TL;DR: This review critically analyzes what is known of phase behavior and liquid-liquid immiscibility in model systems and compares these data with what isknown of domain formation in cell membranes.
Abstract: Views of how cell membranes are organized are presently changing. The lipid bilayer that constitutes these membranes is no longer understood to be a homogeneous fluid. Instead, lipid assemblies, termed rafts, have been introduced to provide fluid platforms that segregate membrane components and dynamically compartmentalize membranes. These assemblies are thought to be composed mainly of sphingolipids and cholesterol in the outer leaflet, somehow connected to domains of unknown composition in the inner leaflet. Specific classes of proteins are associated with the rafts. This review critically analyzes what is known of phase behavior and liquid-liquid immiscibility in model systems and compares these data with what is known of domain formation in cell membranes.

1,615 citations

Journal ArticleDOI
TL;DR: Despite extensive work, the basis for raft formation in cell membranes and the size of rafts and their stability are all uncertain and recent work converges on very small rafts <10 nm in diameter that may enlarge and stabilize when their constituents are cross-linked.
Abstract: ▪ Abstract Lipid raft microdomains were conceived as part of a mechanism for the intracellular trafficking of lipids and lipid-anchored proteins. The raft hypothesis is based on the behavior of defined lipid mixtures in liposomes and other model membranes. Experiments in these well-characterized systems led to operational definitions for lipid rafts in cell membranes. These definitions, detergent solubility to define components of rafts, and sensitivity to cholesterol deprivation to define raft functions implicated sphingolipid- and cholesterol-rich lipid rafts in many cell functions. Despite extensive work, the basis for raft formation in cell membranes and the size of rafts and their stability are all uncertain. Recent work converges on very small rafts <10 nm in diameter that may enlarge and stabilize when their constituents are cross-linked.

1,324 citations


"X-ray and Neutron Scattering Studie..." refers background in this paper

  • ...first biologically relevant molecule whose influence on model membranes was investigated in detail, and over the past few decades there have been a very large number of studies on the influence of cholesterol and other sterols on model membranes using a variety of techniques [8,11,12]....

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