Thermal behavior of synthetic sphingomyelin-cholesterol dispersions

Estep, Timothy N.; Mountcastle, Donald B.; Barenholz, Yechezkel; Biltonen, Rodney L.; Thompson, T. E.

doi:10.1021/bi00577a042

Cited by 160 publications

(89 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, by 1974 a series of biophysical studies started to appear supporting the basic concept of lateral segregation of lipids into microdomains in membranes. Particularly noteworthy were cholesterol-and sphingolipid-enriched domains studied in model bilayer membranes in the 1970s by Biltonen and Thompson [21]. An early differential scanning calorimetry (DSC) study by Demel et al [22] that established differential affinity for cholesterol was based on preferential obliteration by the sterol of melting transitions between two component monotectic lipids.…”

Section: Role Of Cholesterol In Lipid Raftsmentioning

confidence: 99%

The location and behavior of α‐tocopherol in membranes

Atkinson

Harroun

Wassall

et al. 2010

Molecular Nutrition Food Res

168

128

View full text Add to dashboard Cite

Vitamin E (a-tocopherol) has long been recognized as the major antioxidant in biological membranes, and yet many structurally related questions persist of how the vitamin functions. For example, the very low levels of a-tocopherol reported for whole cell extracts question how this molecule can successfully protect the comparatively enormous quantities of PUFAcontaining phospholipids found in membranes that are highly susceptible to oxidative attack. The contemporary realization that membranes laterally segregate into regions of distinct lipid composition (domains), we propose, provides the answer. We hypothesize a-tocopherol partitions into domains that are enriched in polyunsaturated phospholipids, amplifying the concentration of the vitamin in the place where it is most needed. These highly disordered domains depleted in cholesterol are analogous, but organizationally antithetical, to the wellstudied lipid rafts. We review here the ideas that led to our hypothesis. Experimental evidence in support of the formation of PUFA-rich domains in model membranes is presented, focusing upon docosahexaenoic acid that is the most unsaturated fatty acid commonly found. Physical methodologies are then described to elucidate the nature of the interaction of a-tocopherol with PUFA and to establish that the vitamin and PUFA-containing phospholipids co-localize in non-raft domains.

show abstract

Section: Role Of Cholesterol In Lipid Raftsmentioning

confidence: 99%

The location and behavior of α‐tocopherol in membranes

Atkinson

Harroun

Wassall

et al. 2010

Molecular Nutrition Food Res

168

128

View full text Add to dashboard Cite

show abstract

“…Previous physical studies on mixtures of cholesterol with Pam2-PtdCho have suggested the formation of coexisting cholesterol-rich and cholesterol-free domains along the bilayer (4,6,8 (2,8,10) and sphingomyelins (9) have been shown to be composed of broad and sharp components. The broad component, whose contribution is maximal around 15 to 20 mol % cholesterol, has been proposed as evidence for a distinct interfacial region between cholesterol-rich and cholesterol-free domains (8,9). Because the-physical extent of this interfacial region is determined by the lateral distribution of cholesterol, these results provide an appropriate basis for the determination of the lateral organization of cholesterol-phospholipid mixtures.…”

mentioning

confidence: 99%

“…The broad component, whose contribution is maximal around 15 to 20 mol % cholesterol, has been proposed as evidence for a distinct interfacial region between cholesterol-rich and cholesterol-free domains (8,9). Because the-physical extent of this interfacial region is determined by the lateral distribution of cholesterol, these results provide an appropriate basis for the determination of the lateral organization of cholesterol-phospholipid mixtures.…”

mentioning

confidence: 99%

“…These molecular distributions are generated from interaction energies deduced from calorimetric data obtained in this department for cholesterol-phospholipid mixtures (8,9). Direct analysis of the computer-generated lattices yields the lateral distribution of cholesterol molecules as a function of cholesterol concentration, the size of the bilayer, and the magnitude of the interaction energies.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Compositional domain structure in phosphatidylcholine--cholesterol and sphingomyelin--cholesterol bilayers.

Snyder¹,

Freire²

1980

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The lateral distribution of cholesterol in phospholipid bilayers has been investigated through a method of Monte Carlo calculations, using interaction energies deduced from calorimetric results for cholesterol-phospholipid mixtures. Analysis of computer-generated bilayer configurations allows calculation of the spatial localization and relative abundance of distinct regions of varying cholesterol content along the plane of the bilayer. An interfacial phospholipid region between cholesterol-bound and cholesterol-free domains is found to extend one lipid beyond the cholesterol-bound domain for mixtures of cholesterol with palmitoyl sphingomyelin, lignoceroyl sphingomyelin, and dipalmitoyl phosphatidylcholine. The results indicate that the degree of nonideality in the mixing of cholesterol is dependent on fatty acid chain length and that cholesterol mixes more ideally in sphingomyelins than in phosphatidylcholines of equal chain length. It is found that at ;20 mol % cholesterol the cholesterol-rich areas suddenly become connected, forming a network that extends over the entire bila er. This change in the lateral connectivity of the cholesterol-rich domains occurs over a narrow concentration interval and is presumably responsible for the abrupt change in the lateral diffusion coefficient observed at this concentration. In the past few years numerous physical studies have attempted to characterize the interactions of cholesterol with phosphatidylcholines and sphingomyelins (1). These major lipid components have been of interest due to the fundamental role they play in the regulation of the molecular and macroscopic properties of biological membranes. The common elements found in most studies of cholesterol-phospholipid mixtures have been breaks or discontinuities in behavior at concentrations ranging from 7.5 to 50 mol % cholesterol (2). These discontinuities have been interpreted from a molecular point of view, as evidence for the formation of cholesterol-phospholipid complexes of specific stoichiometry (3-5), or from a macroscopic point of view, as an indication of phase boundaries in the construction of phase diagrams for these mixtures (2, 6). Only recently have attempts been made to correlate molecular properties with macroscopic phase behavior from a unified point of view. In this respect, Pink and Chapman (7) successfully predicted the dependence of the transition enthalpy of dipalmitoyl phosphatidylcholine (Pam2-PtdCho) on the mole fraction of cholesterol; however, those mean field calculations were directed towards evaluating overall thermodynamic parameters and as such provided no information regarding the distribution of cholesterol and distinct phospholipid species within the bilayer.In order to fully characterize the interactions of cholesterol with phospholipid bilayers, it will be necessary to develop a quantitative description of the distribution of cholesterol within the bilayer and the relationship of this distribution with ex- (9) have been shown to be composed of broad and sharp componen...

show abstract

“…Several recent findings single out sphingolipids as having important effects on membrane fluidity (48)(49)(50). In addition, sphingolipids in general appear to have a unique relationship with sterols, and it has been suggested that these two lipids form a complex (51)(52)(53)(54)(55). As shown here, the baA mutation alters the sphingolipid composition, which may then alter the fluidity of the ciliary membrane under specific environmental conditions and, thus, the functioning ofthe ion channels.…”

Section: Discussionmentioning

confidence: 99%

Mutational alteration of membrane phospholipid composition and voltage-sensitive ion channel function in paramecium.

Forte¹,

Satow²,

Nelson³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A behavioral mutant of Paramecium tetraurelia (baA) has been isolated that has an abnormal response when placed in solutions containing Ba2+. This mutant is shown here to have a dramatic alteration of the sphingolipid and phosphonolipid composition ofits ciliary membrane. This biochemical defect is present in independently isolated alleles at baA locus and segregates in crosses with the behavioral phenotype. Electrophysiologically, the mutation reduces significantly conductance of both voltage-sensitive Ca2+ channels and voltage-sensitive K+ channels. When the mutant is grown in sterol-supplemented medium, its behavior, electrophysiological properties, and lipid composition are hardly distinguishable from wild type grown under similar conditions. This mutant then, provides strong evidence that membrane lipids significantly influence the function of the membrane molecules responsible for the generation of action potentials.Many membrane enzymatic and transport functions have been shown to be modulated by the membrane lipid composition (1-3). The membrane proteins responsible for the generation of action potentials are similar to those with enzymatic activity in that their function is influenced by membrane lipids as inferred from indirect studies on the effects of temperature (4), enzyme digestions (5-9), and the application of agents (e.g., local anesthetics or pressure), which are expected to alter the physical properties of membrane lipid (10-13).The ciliated protozoan Paramecium tetraurelia is well suited to the study ofthe molecular basis ofmembrane excitability. The cilia of Paramecium are covered by a membrane that is continuous with the body surface membrane (14). Membrane depolarization causes these channels to open allowing an influx of Ca2+, which increases transiently the intracellular Ca2+ concentration, reversing the direction ofthe ciliary beat and swimming direction (15,16 (33), and hydrostatic pressure (34) have suggested that lipids also affect ion channel activity in Paramecium. In this report we now show that the functions ofvoltage-sensitive ion channels in the excitable membrane of Paramecium appear to be affected by a mutationally induced change in the phospholipid composition of the ciliary membrane. This mutant provides strong evidence that membrane lipids significantly influence the function of membrane proteins responsible for the generation of action potentials. METHODSCulture Conditions and Stocks. Cells were grown by routine methods (21, 35). H332PO4 was added to 0.5 /Ci/ml (1 Ci = 3.7 x 1010 becquerels) prior to addition of bacteria to the medium. In some cases stigmasterol (5 mg/liter) was also added to the medium prior to bacteria addition. The strains were: wild type, 51s; baA-i, d4-592; baA-2, d4-593; baA-3, d4-594; fna, d4-91; pwA, d4-94; baB, d5-599 (27).Cilia Isolation and Lipid Extraction. Cells in late logarithmic growth were harvested, washed extensively, and deciliated; the cilia were separated from bodies as described by Adoutte et al (25). Lipids were extracted...

show abstract

Thermal behavior of synthetic sphingomyelin-cholesterol dispersions

Cited by 160 publications

References 29 publications

The location and behavior of α‐tocopherol in membranes

The location and behavior of α‐tocopherol in membranes

Compositional domain structure in phosphatidylcholine--cholesterol and sphingomyelin--cholesterol bilayers.

Mutational alteration of membrane phospholipid composition and voltage-sensitive ion channel function in paramecium.

Contact Info

Product

Resources

About