David A Mannock | University of Alberta (original) (raw)

Papers by David A Mannock

Eureka

Studying the nature of interactions between the sterol ring system and neigbouring phospholipid m... more Studying the nature of interactions between the sterol ring system and neigbouring phospholipid molecules is important for our understanding of the properties of sterols in biological molecules and the role of such interactions in many disease processes. In this project, the thermotropic phase behaviour of binary dipalmitoylphosphatidylcholine (DPPC)/sterol mixtures with different sterol ring configurations (C5,6 double bond, 5α-H and 5β-H orientation and either 3α-OH, 3β-OH, 3-ketone functional groups) was investigated using differential scanning calorimetry (DSC) and was compared to earlier studies of cholesterol/ and epicholesterol/DPPC mixtures. Given the differences in the thermodynamic parameters obtained from these mixtures and their associated changes in bilayer stability and miscibility, it is clear that changing the sterol chemical configuration has a significant effect on bilayer properties. Any sterol molecule whose ring structure deviates from that of cholesterol is unl...

Biochemistry, 1990

The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O... more The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerols was studied by differential scanning calorimetry. At fast heating rates unannealed samples of these lipids exhibit a strongly energetic transition, which has been identified as a lamellar gel/liquid crystalline (L beta/L alpha) phase transition (short- and medium-chain compounds) or a lamellar gel to inverted hexagonal (L beta/HII) phase transition (long-chain compounds) by X-ray diffraction studies (Sen et al., 1990). At still higher temperatures, some of the lipids that form lamellar liquid-crystalline phases exhibit an additional transition, which has been identified as a transition to an inverted nonbilayer phase by X-ray diffraction studies. The lamellar gel phase formed on initial cooling of these lipids is a metastable structure, which, when annealed under appropriate conditions, transforms to a more stable lamellar gel phase, which has been identified as a poorly hydrated crystal-like phase with tilted acyl chains by X-ray diffraction measurements (Sen et al., 1990). With the exception of the di-19:0 homologue, the crystalline phases of these lipids are stable to temperatures higher than those at which their L beta phases melt and, as a result, they convert directly to L alpha or HII phases on heating. Our results indicate that the length of the acyl chain affects both the kinetic and thermodynamic properties of the crystalline phases of these lipids as well as the type of nonbilayer phase that they form. Moreover, when compared with the beta-anomers, these alpha-D-glucosyl diacylglycerols are more prone to form ordered crystalline gel phases at low temperatures and are somewhat less prone to form nonbilayer phases at elevated temperatures. Thus the physical properties of glucolipids (and possibly all glycolipids) are very sensitive to the nature of the anomeric linkage between the sugar headgroup and the glycerol backbone of the lipid molecule. We suggest that this is, in part, due to a change in orientation of the glucopyranosyl ring relative to the bilayer surface, which in turn affects the way(s) in which the sugar headgroups interact with each other and with water.

Biochemistry Usa, 1990

The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O... more The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerols was studied by differential scanning calorimetry. At fast heating rates unannealed samples of these lipids exhibit a strongly energetic transition, which has been identified as a lamellar gel/liquid crystalline (L beta/L alpha) phase transition (short- and medium-chain compounds) or a lamellar gel to inverted hexagonal (L beta/HII) phase transition (long-chain compounds) by X-ray diffraction studies (Sen et al., 1990). At still higher temperatures, some of the lipids that form lamellar liquid-crystalline phases exhibit an additional transition, which has been identified as a transition to an inverted nonbilayer phase by X-ray diffraction studies. The lamellar gel phase formed on initial cooling of these lipids is a metastable structure, which, when annealed under appropriate conditions, transforms to a more stable lamellar gel phase, which has been identified as a poorly hydrated crystal-like phase with tilted acyl chains by X-ray diffraction measurements (Sen et al., 1990). With the exception of the di-19:0 homologue, the crystalline phases of these lipids are stable to temperatures higher than those at which their L beta phases melt and, as a result, they convert directly to L alpha or HII phases on heating. Our results indicate that the length of the acyl chain affects both the kinetic and thermodynamic properties of the crystalline phases of these lipids as well as the type of nonbilayer phase that they form. Moreover, when compared with the beta-anomers, these alpha-D-glucosyl diacylglycerols are more prone to form ordered crystalline gel phases at low temperatures and are somewhat less prone to form nonbilayer phases at elevated temperatures. Thus the physical properties of glucolipids (and possibly all glycolipids) are very sensitive to the nature of the anomeric linkage between the sugar headgroup and the glycerol backbone of the lipid molecule. We suggest that this is, in part, due to a change in orientation of the glucopyranosyl ring relative to the bilayer surface, which in turn affects the way(s) in which the sugar headgroups interact with each other and with water.

Journal De Physique Ii, 1992

... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic ph... more ... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic phases of di-dodecyl alkyl-pD-glucopyranosyl-rac-glycerol David C. Turner (~>*) Zhen-Gang Wang (2), Sol M. Gruner (~), David A. Mannock (~) and Ronald N. McElhaney (3) * ...

Journal of Physics B Atomic and Molecular Physics, 1992

... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic ph... more ... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic phases of di-dodecyl alkyl-pD-glucopyranosyl-rac-glycerol David C. Turner (~>*) Zhen-Gang Wang (2), Sol M. Gruner (~), David A. Mannock (~) and Ronald N. McElhaney (3) * ...

Biochemistry, 1988

The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O... more The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerols was studied by differential scanning calorimetry. At fast heating rates unannealed samples of these lipids exhibit a strongly energetic transition, which has been identified as a lamellar gel/liquid crystalline (L beta/L alpha) phase transition (short- and medium-chain compounds) or a lamellar gel to inverted hexagonal (L beta/HII) phase transition (long-chain compounds) by X-ray diffraction studies (Sen et al., 1990). At still higher temperatures, some of the lipids that form lamellar liquid-crystalline phases exhibit an additional transition, which has been identified as a transition to an inverted nonbilayer phase by X-ray diffraction studies. The lamellar gel phase formed on initial cooling of these lipids is a metastable structure, which, when annealed under appropriate conditions, transforms to a more stable lamellar gel phase, which has been identified as a poorly hydrated crystal-like phase with tilted acyl chains by X-ray diffraction measurements (Sen et al., 1990). With the exception of the di-19:0 homologue, the crystalline phases of these lipids are stable to temperatures higher than those at which their L beta phases melt and, as a result, they convert directly to L alpha or HII phases on heating. Our results indicate that the length of the acyl chain affects both the kinetic and thermodynamic properties of the crystalline phases of these lipids as well as the type of nonbilayer phase that they form. Moreover, when compared with the beta-anomers, these alpha-D-glucosyl diacylglycerols are more prone to form ordered crystalline gel phases at low temperatures and are somewhat less prone to form nonbilayer phases at elevated temperatures. Thus the physical properties of glucolipids (and possibly all glycolipids) are very sensitive to the nature of the anomeric linkage between the sugar headgroup and the glycerol backbone of the lipid molecule. We suggest that this is, in part, due to a change in orientation of the glucopyranosyl ring relative to the bilayer surface, which in turn affects the way(s) in which the sugar headgroups interact with each other and with water.

Biochemistry Usa, 1990

The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O... more The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerols was studied by differential scanning calorimetry. At fast heating rates unannealed samples of these lipids exhibit a strongly energetic transition, which has been identified as a lamellar gel/liquid crystalline (L beta/L alpha) phase transition (short- and medium-chain compounds) or a lamellar gel to inverted hexagonal (L beta/HII) phase transition (long-chain compounds) by X-ray diffraction studies (Sen et al., 1990). At still higher temperatures, some of the lipids that form lamellar liquid-crystalline phases exhibit an additional transition, which has been identified as a transition to an inverted nonbilayer phase by X-ray diffraction studies. The lamellar gel phase formed on initial cooling of these lipids is a metastable structure, which, when annealed under appropriate conditions, transforms to a more stable lamellar gel phase, which has been identified as a poorly hydrated crystal-like phase with tilted acyl chains by X-ray diffraction measurements (Sen et al., 1990). With the exception of the di-19:0 homologue, the crystalline phases of these lipids are stable to temperatures higher than those at which their L beta phases melt and, as a result, they convert directly to L alpha or HII phases on heating. Our results indicate that the length of the acyl chain affects both the kinetic and thermodynamic properties of the crystalline phases of these lipids as well as the type of nonbilayer phase that they form. Moreover, when compared with the beta-anomers, these alpha-D-glucosyl diacylglycerols are more prone to form ordered crystalline gel phases at low temperatures and are somewhat less prone to form nonbilayer phases at elevated temperatures. Thus the physical properties of glucolipids (and possibly all glycolipids) are very sensitive to the nature of the anomeric linkage between the sugar headgroup and the glycerol backbone of the lipid molecule. We suggest that this is, in part, due to a change in orientation of the glucopyranosyl ring relative to the bilayer surface, which in turn affects the way(s) in which the sugar headgroups interact with each other and with water.

Biophysical Journal, 1994

We have investigated the thermotropic phase behavior of aqueous dispersions of the 1,2- and 2,3-d... more We have investigated the thermotropic phase behavior of aqueous dispersions of the 1,2- and 2,3-di-O-tetradecyl-1(3)-O-(beta-D-galactopyranosyl)-sn- glycerols and their diastereomeric mixture using differential scanning calorimetry and low-angle and wide-angle x-ray diffraction. Upon heating, unannealed aqueous dispersions of these compounds all exhibit a lower temperature, moderately energetic phase transition at approximately 52 degrees C and a higher temperature, weakly energetic phase transition at approximately 63 degrees C, both of which are reversible on cooling. X-ray diffraction measurements identify these events as the L beta (or L' beta)/L alpha and L alpha/HII phase transitions, respectively. The structures of the L beta, L alpha, and HII phases of these lipids, as determined by x-ray diffraction measurements, are identical within the error bars for all of these lipids. On annealing below the L beta/L alpha phase transition temperature, the L beta phase converts to an Lc phase at a rate which is strongly dependent on the chirality of the glycerol backbone (1,2-sn > 1,2-rac > 2,3-sn). The temperature of the phase transition from the Lc phase seen on reheating is also dependent on the glycerol chirality. In addition, the nature of the Lc phase changes on subsequent heating in the 1,2-sn and 1,2-rac lipids, but we have not been able to detect this Lc1/Lc2 phase transition by calorimetry. However, wide-angle x-ray diffraction measurements indicate that these Lc phases differ mostly in their hydrocarbon chain packing modes. The Lc2 phase does not appear to be present in the 2,3-sn compound, suggesting that its formation is not favored in this diastereomeric isomer. These observations are discussed in relation to the effect of glycerol chirality on the molecular packing of these glycolipids, particularly on hydrogen bonding and hydration in the interfacial region of the bilayer.

Journal De Physique Ii, Nov 1, 1992

... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic ph... more ... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic phases of di-dodecyl alkyl-pD-glucopyranosyl-rac-glycerol David C. Turner (~>*) Zhen-Gang Wang (2), Sol M. Gruner (~), David A. Mannock (~) and Ronald N. McElhaney (3) * ...

European biophysics journal : EBJ, 2001

The lamellar gel to lamellar liquid-crystalline (Lbeta/Lalpha) and lamellar liquid-crystalline to... more The lamellar gel to lamellar liquid-crystalline (Lbeta/Lalpha) and lamellar liquid-crystalline to inverted hexagonal (Lalpha/H(II)) phase transitions of a number of phosphatidylethanolamines (PEs) and diacyl-alpha-D-glucosyl-sn-glycerols (alpha-D-GlcDAGs) containing linear saturated, linear unsaturated, branched or alicyclic hydrocarbon chains of various lengths were examined by differential scanning calorimetry and low-angle X-ray diffraction. As reported previously, for each homologous series of PEs or alpha-D-GlcDAGs, the Lbeta/Lalpha phase transition temperatures (Tm) increase and the Lalpha/H(II) phase transition temperatures (Th) decrease with increases in hydrocarbon chain length. The Tm and the especially the Th values for the PEs are higher than those of the corresponding alpha-D-GlcDAGs. For PEs having the same effective hydrocarbon chain length but different chain configurations, the Tm and Th values vary markedly but with an almost constant temperature interval (deltaT(L...

Biochemical Journal

Glucocerebrosidase, the lysosomal enzyme that is deficient in patients with Gaucher's disease... more Glucocerebrosidase, the lysosomal enzyme that is deficient in patients with Gaucher's disease, hydrolyses non-physiological aryl beta-D-glucosides and glucocerebroside, its substrate in vivo. We document that 2,3,-di-O-tetradecyl-1-O-(beta-D-glucopyranosyl)-sn-glycerol (2,3,-di-14:0-beta-Glc-DAG) inhibits human placental glucocerebrosidase activity in vitro (Ki 0.18 mM), and the nature of inhibition is typical of a mixed-type pattern. Furthermore, 2,3-di-14:0-beta-Glc-DAG was shown to be an excellent substrate for the lysosomal beta-glucosidase (Km 0.15 mM; Vmax. 19.8 units/mg) when compared with the natural substrate glucocerebroside (Km 0.080 mM; Vmax. 10.4 units/mg). The observations that (i) glucocerebrosidase-catalysed hydrolysis of 2,3-di-14:0-beta-Glc-DAG is inhibited by conduritol B epoxide and glucosylsphingosine, and (ii) spleen and brain extracts from patients with Gaucher's disease are unable to hydrolyse 2,3-di-14:O-beta-Glc-DAG demonstrate that the same active ...

Journal de Physique II, 1992

... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic ph... more ... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic phases of di-dodecyl alkyl-pD-glucopyranosyl-rac-glycerol David C. Turner (~>*) Zhen-Gang Wang (2), Sol M. Gruner (~), David A. Mannock (~) and Ronald N. McElhaney (3) * ...

Current Topics in Membranes, 1997

Molecular Crystals and Liquid Crystals, 2003

We have used X-ray diffraction and differential scanning calorimetry (DSC) to study the structure... more We have used X-ray diffraction and differential scanning calorimetry (DSC) to study the structure and lyotropic phase behaviour of two synthetic dialkyl glycolipids having β-D-glucose and β-D-galactose headgroups and two saturated tetradecyl (C14) chains. The diastereomeric compounds, 1,2-di-O-tetradecyl-3-O-(β-D-glucopyranosyl)-sn-glycerol (di-14:0–β-D-GlcDAG) and 1,2-di-O-tetradecyl-3-O-(β-D-galactopyranosyl)-sn-glycerol (di-14:0-β-D-GalDAG) show striking differences in their phase behaviour, particularly in the ordered lamellar phase region. Both compounds adopt the fluid lamellar Lα phase upon cooling from the HII phase, but below the chain-melting transition,di-14:0-β-D-GlcDAG forms a metastable Lβ gel phase, whereas di-14:0–β-D-GalDAG forms only crystalline lamellar phases, on the timescale of our measurements. We have determined the limiting hydrations of the various phases, and compare the findings from these glycolipids with those from our previous studies of the phospholipid didodecyl phosphatidylethanolamine (di-12:0-PE).

Langmuir, 1997

ABSTRACT We report on the effects of hydrostatic pressure and temperature on the phase and struct... more ABSTRACT We report on the effects of hydrostatic pressure and temperature on the phase and structural behavior of the complete range of the known, excess water, inverse lyotropic mesophases. This range of interfacial topologies is exhibited by homologous series of saturated C12, C14, and C16 dialkyl phosphatidylethanolamines (PE) and saturated C12 and C16 dialkyl xylopyranosylglycerols (xylolipids) in the p−T region 0−2.5 kbar and 30−130 °C. The PEs cover the mesophases with gentle interfacial curvature while the xylolipids cover the more curved mesophases. We demonstrate that temperature and pressure have noncongruent effects on the structural and the phase behavior. Quantitatively, mesophase lattice parameters and phase boundaries show small but observable differences in their functional dependence on pressure and temperature. Qualitatively, increasing pressure stabilizes inverse bicontinuous cubic phases in C14 PE. At atmospheric pressure only the C12 PE contains such phases. Conversely we find that increasing pressure destabilizes the inverse micellar cubic phase observed in the C16 xylolipid. In general a trend is seen for a stronger pressure effect in eliminating phases with larger packing costs, which we infer is due to differences in the effects of pressure and temperature on the monolayer's spontaneous mean curvature and its bending rigidity.

Chemistry and Physics of Lipids, 2002

The large intrinsic membrane dipole potential, b d , is important for protein insertion and funct... more The large intrinsic membrane dipole potential, b d , is important for protein insertion and functioning as well as for ion transport across natural and model membranes. However, the origin of b d is controversial. From experiments carried out with lipid monolayers, a significant dependence on the fatty acid chain length is suggested, whereas in experiments with lipid bilayers, the contribution of additional CH 2 -groups seems negligibly small compared with that of the phospholipid carbonyl groups and lipid-bound water molecules. To compare the impact of the CH 2 -groups of dipalmitoylphosphatidylcholine (DPPC) near and far from the glycerol backbone, we have varied the structure of DPPC by incorporation of sulfur atoms in place of methylene groups in different positions of the fatty acid chain. The b d of symmetric lipid bilayers containing one heteroatom was obtained from the charge relaxation of oppositely charged hydrophobic ions. We have found that the substitution for a S-atom of a CH 2 -group decreases b d . The effect (Db d = −22.6 mV) is most pronounced for S-atoms near the lipid head group while a S-atom substitution in the C 13 -or C 14 -position of the hydrocarbon chain does not effect the bilayer dipole potential. Most probably Db d does not originate from an altered dipole potential of the acyl chain containing an heteroatom but is mediated by the disruption of chain packing, leading to a decreased density of lipid dipoles in the membrane. : S 0 0 0 9 -3 0 8 4 ( 0 2 ) 0 0 0 1 3 -0 U. Peterson et al. /

Chemistry and Physics of Lipids, 2010

This review deals with the effect of variations in phospholipid and sterol structure on the natur... more This review deals with the effect of variations in phospholipid and sterol structure on the nature and magnitude of lipid-sterol interactions in lipid bilayer model membranes. The first portion of the review covers the effect of Chol itself on the thermotropic phase behavior and organization of a variety of different glycero-and sphingolipid membrane lipid classes, varying in the structure and charge of their polar headgroups and in the length and structure of their fatty acyl chains. The second part of this review deals with the effect of variations in sterol structure on the thermotropic phase behavior and organization primarily of the well studied DPPC model membrane system. In the third section, we focus on some of the contributions of sterol functional group chemistry, molecular conformation and dynamics, to sterollipid interactions. Using those studies, we re-examine the results of recently published experimental and computer-modeling studies to provide a new more dynamic molecular interpretation of sterol-lipid interactions. We suggest that the established view of the rigid sterol ring system and extended alkyl side-chain obtained from physical studies of cholesterol-phospholipid mixtures may not apply in lipid mixtures differing in their sterol chemical structure. L is lauroyl, M is myristoyl, P is palmitoyl, S is stearoyl, A is arachidoyl, E is elaidoyl and O is oleoyl (DMPC is dimyristoylphosphatidylcholine, etc.); LC , lamellar crystalline phase with tilted hydrocarbon chains; L ␤ or L ␤ , planar lamellar gel state with tilted or untilted hydrocarbon chains, respectively; P ␤ , rippled gel state with titled hydrocarbon chains; L␣, lamellar liquid-crystalline state; Lo or L d , lamellar liquid-ordered or liquid-disordered state, respectively; Tp and Tm, the pretransition and main phase transition temperature, respectively; Hp and Hm, enthalpy of the pretransition and main phase transition, respectively; T 1/2 , width of the DSC endotherm at half height ( • C), which is inversely related to the cooperativity of the phase transition; Tm shp , phase transition temperature of the sharp component of the DSC endotherm corresponding to the sterol-poor bilayer regions; Tm brd , phase transition temperature of the broad component of the DSC endotherm corresponding to the sterol-rich bilayer regions; Hm shp , phase transition enthalpy of the sharp component of the DSC endotherm corresponding to the sterol-poor bilayer regions; Hm brd , phase transition enthalpy of the broad component of the DSC endotherm corresponding to the sterol-rich bilayer regions; DSC, differential scanning calorimetry; FTIR, Fourier transform infrared; NMR, nuclear magnetic resonance.

Chemistry and Physics of Lipids, 2007

The thermotropic phase behaviour of aqueous dispersions of some synthetic 1,2-di-O-alkyl-3-O-(␤-d... more The thermotropic phase behaviour of aqueous dispersions of some synthetic 1,2-di-O-alkyl-3-O-(␤-d-galactosyl)-rac-glycerols (rac-␤-d-GalDAGs) with both odd and even hydrocarbon chain lengths was studied by differential scanning calorimetry (DSC), small-angle (SAXS) and wide-angle (WAXS) X-ray diffraction. DSC heating curves show a complex pattern of lamellar (L) and nonlamellar (NL) phase polymorphism dependent on the sample's thermal history. On cooling from 95 • C and immediate reheating, rac-␤-d-GalDAGs typically show a single, strongly energetic phase transition, corresponding to either a lamellar gel/liquid-crystalline (L ␤ /L ␣ ) phase transition (N ≤ 15 carbon atoms) or a lamellar gel/inverted hexagonal (L ␤ /H II ) phase transition (N ≥ 16). At higher temperatures, some shorter chain compounds (N = 10-13) exhibit additional endothermic phase transitions, identified as L/NL phase transitions using SAXS/WAXS. The NL morphology and the number of associated intermediate transitions vary with hydrocarbon chain length. Typically, at temperatures just above the L ␣ phase boundary, a region of phase coexistence consisting of two inverted cubic (Q II ) phases are observed. The space group of the cubic phase seen on initial heating has not been determined; however, on further heating, this Q II phase disappears, enabling the identification of the second Q II phase as Pn3m (space group Q 224 ). Only the Pn3m phase is seen on cooling.

Chemistry and Physics of Lipids, 2011

Epicoprostanol Phosphatidylcholine Sterol-lipid interactions Phospholipid thermotropic phase beha... more Epicoprostanol Phosphatidylcholine Sterol-lipid interactions Phospholipid thermotropic phase behaviour Differential scanning calorimetry a b s t r a c t

Eureka

Studying the nature of interactions between the sterol ring system and neigbouring phospholipid m... more Studying the nature of interactions between the sterol ring system and neigbouring phospholipid molecules is important for our understanding of the properties of sterols in biological molecules and the role of such interactions in many disease processes. In this project, the thermotropic phase behaviour of binary dipalmitoylphosphatidylcholine (DPPC)/sterol mixtures with different sterol ring configurations (C5,6 double bond, 5α-H and 5β-H orientation and either 3α-OH, 3β-OH, 3-ketone functional groups) was investigated using differential scanning calorimetry (DSC) and was compared to earlier studies of cholesterol/ and epicholesterol/DPPC mixtures. Given the differences in the thermodynamic parameters obtained from these mixtures and their associated changes in bilayer stability and miscibility, it is clear that changing the sterol chemical configuration has a significant effect on bilayer properties. Any sterol molecule whose ring structure deviates from that of cholesterol is unl...

Biochemistry, 1990

The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O... more The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerols was studied by differential scanning calorimetry. At fast heating rates unannealed samples of these lipids exhibit a strongly energetic transition, which has been identified as a lamellar gel/liquid crystalline (L beta/L alpha) phase transition (short- and medium-chain compounds) or a lamellar gel to inverted hexagonal (L beta/HII) phase transition (long-chain compounds) by X-ray diffraction studies (Sen et al., 1990). At still higher temperatures, some of the lipids that form lamellar liquid-crystalline phases exhibit an additional transition, which has been identified as a transition to an inverted nonbilayer phase by X-ray diffraction studies. The lamellar gel phase formed on initial cooling of these lipids is a metastable structure, which, when annealed under appropriate conditions, transforms to a more stable lamellar gel phase, which has been identified as a poorly hydrated crystal-like phase with tilted acyl chains by X-ray diffraction measurements (Sen et al., 1990). With the exception of the di-19:0 homologue, the crystalline phases of these lipids are stable to temperatures higher than those at which their L beta phases melt and, as a result, they convert directly to L alpha or HII phases on heating. Our results indicate that the length of the acyl chain affects both the kinetic and thermodynamic properties of the crystalline phases of these lipids as well as the type of nonbilayer phase that they form. Moreover, when compared with the beta-anomers, these alpha-D-glucosyl diacylglycerols are more prone to form ordered crystalline gel phases at low temperatures and are somewhat less prone to form nonbilayer phases at elevated temperatures. Thus the physical properties of glucolipids (and possibly all glycolipids) are very sensitive to the nature of the anomeric linkage between the sugar headgroup and the glycerol backbone of the lipid molecule. We suggest that this is, in part, due to a change in orientation of the glucopyranosyl ring relative to the bilayer surface, which in turn affects the way(s) in which the sugar headgroups interact with each other and with water.

Biochemistry Usa, 1990

The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O... more The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerols was studied by differential scanning calorimetry. At fast heating rates unannealed samples of these lipids exhibit a strongly energetic transition, which has been identified as a lamellar gel/liquid crystalline (L beta/L alpha) phase transition (short- and medium-chain compounds) or a lamellar gel to inverted hexagonal (L beta/HII) phase transition (long-chain compounds) by X-ray diffraction studies (Sen et al., 1990). At still higher temperatures, some of the lipids that form lamellar liquid-crystalline phases exhibit an additional transition, which has been identified as a transition to an inverted nonbilayer phase by X-ray diffraction studies. The lamellar gel phase formed on initial cooling of these lipids is a metastable structure, which, when annealed under appropriate conditions, transforms to a more stable lamellar gel phase, which has been identified as a poorly hydrated crystal-like phase with tilted acyl chains by X-ray diffraction measurements (Sen et al., 1990). With the exception of the di-19:0 homologue, the crystalline phases of these lipids are stable to temperatures higher than those at which their L beta phases melt and, as a result, they convert directly to L alpha or HII phases on heating. Our results indicate that the length of the acyl chain affects both the kinetic and thermodynamic properties of the crystalline phases of these lipids as well as the type of nonbilayer phase that they form. Moreover, when compared with the beta-anomers, these alpha-D-glucosyl diacylglycerols are more prone to form ordered crystalline gel phases at low temperatures and are somewhat less prone to form nonbilayer phases at elevated temperatures. Thus the physical properties of glucolipids (and possibly all glycolipids) are very sensitive to the nature of the anomeric linkage between the sugar headgroup and the glycerol backbone of the lipid molecule. We suggest that this is, in part, due to a change in orientation of the glucopyranosyl ring relative to the bilayer surface, which in turn affects the way(s) in which the sugar headgroups interact with each other and with water.

Journal De Physique Ii, 1992

... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic ph... more ... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic phases of di-dodecyl alkyl-pD-glucopyranosyl-rac-glycerol David C. Turner (~>*) Zhen-Gang Wang (2), Sol M. Gruner (~), David A. Mannock (~) and Ronald N. McElhaney (3) * ...

Journal of Physics B Atomic and Molecular Physics, 1992

... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic ph... more ... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic phases of di-dodecyl alkyl-pD-glucopyranosyl-rac-glycerol David C. Turner (~>*) Zhen-Gang Wang (2), Sol M. Gruner (~), David A. Mannock (~) and Ronald N. McElhaney (3) * ...

Biochemistry, 1988

The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O... more The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerols was studied by differential scanning calorimetry. At fast heating rates unannealed samples of these lipids exhibit a strongly energetic transition, which has been identified as a lamellar gel/liquid crystalline (L beta/L alpha) phase transition (short- and medium-chain compounds) or a lamellar gel to inverted hexagonal (L beta/HII) phase transition (long-chain compounds) by X-ray diffraction studies (Sen et al., 1990). At still higher temperatures, some of the lipids that form lamellar liquid-crystalline phases exhibit an additional transition, which has been identified as a transition to an inverted nonbilayer phase by X-ray diffraction studies. The lamellar gel phase formed on initial cooling of these lipids is a metastable structure, which, when annealed under appropriate conditions, transforms to a more stable lamellar gel phase, which has been identified as a poorly hydrated crystal-like phase with tilted acyl chains by X-ray diffraction measurements (Sen et al., 1990). With the exception of the di-19:0 homologue, the crystalline phases of these lipids are stable to temperatures higher than those at which their L beta phases melt and, as a result, they convert directly to L alpha or HII phases on heating. Our results indicate that the length of the acyl chain affects both the kinetic and thermodynamic properties of the crystalline phases of these lipids as well as the type of nonbilayer phase that they form. Moreover, when compared with the beta-anomers, these alpha-D-glucosyl diacylglycerols are more prone to form ordered crystalline gel phases at low temperatures and are somewhat less prone to form nonbilayer phases at elevated temperatures. Thus the physical properties of glucolipids (and possibly all glycolipids) are very sensitive to the nature of the anomeric linkage between the sugar headgroup and the glycerol backbone of the lipid molecule. We suggest that this is, in part, due to a change in orientation of the glucopyranosyl ring relative to the bilayer surface, which in turn affects the way(s) in which the sugar headgroups interact with each other and with water.

Biochemistry Usa, 1990

The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O... more The polymorphic phase behavior of aqueous dispersions of a homologous series of 1,2-di-O-acyl-3-O-(alpha-D-glucopyranosyl)-sn-glycerols was studied by differential scanning calorimetry. At fast heating rates unannealed samples of these lipids exhibit a strongly energetic transition, which has been identified as a lamellar gel/liquid crystalline (L beta/L alpha) phase transition (short- and medium-chain compounds) or a lamellar gel to inverted hexagonal (L beta/HII) phase transition (long-chain compounds) by X-ray diffraction studies (Sen et al., 1990). At still higher temperatures, some of the lipids that form lamellar liquid-crystalline phases exhibit an additional transition, which has been identified as a transition to an inverted nonbilayer phase by X-ray diffraction studies. The lamellar gel phase formed on initial cooling of these lipids is a metastable structure, which, when annealed under appropriate conditions, transforms to a more stable lamellar gel phase, which has been identified as a poorly hydrated crystal-like phase with tilted acyl chains by X-ray diffraction measurements (Sen et al., 1990). With the exception of the di-19:0 homologue, the crystalline phases of these lipids are stable to temperatures higher than those at which their L beta phases melt and, as a result, they convert directly to L alpha or HII phases on heating. Our results indicate that the length of the acyl chain affects both the kinetic and thermodynamic properties of the crystalline phases of these lipids as well as the type of nonbilayer phase that they form. Moreover, when compared with the beta-anomers, these alpha-D-glucosyl diacylglycerols are more prone to form ordered crystalline gel phases at low temperatures and are somewhat less prone to form nonbilayer phases at elevated temperatures. Thus the physical properties of glucolipids (and possibly all glycolipids) are very sensitive to the nature of the anomeric linkage between the sugar headgroup and the glycerol backbone of the lipid molecule. We suggest that this is, in part, due to a change in orientation of the glucopyranosyl ring relative to the bilayer surface, which in turn affects the way(s) in which the sugar headgroups interact with each other and with water.

Biophysical Journal, 1994

We have investigated the thermotropic phase behavior of aqueous dispersions of the 1,2- and 2,3-d... more We have investigated the thermotropic phase behavior of aqueous dispersions of the 1,2- and 2,3-di-O-tetradecyl-1(3)-O-(beta-D-galactopyranosyl)-sn- glycerols and their diastereomeric mixture using differential scanning calorimetry and low-angle and wide-angle x-ray diffraction. Upon heating, unannealed aqueous dispersions of these compounds all exhibit a lower temperature, moderately energetic phase transition at approximately 52 degrees C and a higher temperature, weakly energetic phase transition at approximately 63 degrees C, both of which are reversible on cooling. X-ray diffraction measurements identify these events as the L beta (or L' beta)/L alpha and L alpha/HII phase transitions, respectively. The structures of the L beta, L alpha, and HII phases of these lipids, as determined by x-ray diffraction measurements, are identical within the error bars for all of these lipids. On annealing below the L beta/L alpha phase transition temperature, the L beta phase converts to an Lc phase at a rate which is strongly dependent on the chirality of the glycerol backbone (1,2-sn > 1,2-rac > 2,3-sn). The temperature of the phase transition from the Lc phase seen on reheating is also dependent on the glycerol chirality. In addition, the nature of the Lc phase changes on subsequent heating in the 1,2-sn and 1,2-rac lipids, but we have not been able to detect this Lc1/Lc2 phase transition by calorimetry. However, wide-angle x-ray diffraction measurements indicate that these Lc phases differ mostly in their hydrocarbon chain packing modes. The Lc2 phase does not appear to be present in the 2,3-sn compound, suggesting that its formation is not favored in this diastereomeric isomer. These observations are discussed in relation to the effect of glycerol chirality on the molecular packing of these glycolipids, particularly on hydrogen bonding and hydration in the interfacial region of the bilayer.

Journal De Physique Ii, Nov 1, 1992

... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic ph... more ... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic phases of di-dodecyl alkyl-pD-glucopyranosyl-rac-glycerol David C. Turner (~>*) Zhen-Gang Wang (2), Sol M. Gruner (~), David A. Mannock (~) and Ronald N. McElhaney (3) * ...

European biophysics journal : EBJ, 2001

The lamellar gel to lamellar liquid-crystalline (Lbeta/Lalpha) and lamellar liquid-crystalline to... more The lamellar gel to lamellar liquid-crystalline (Lbeta/Lalpha) and lamellar liquid-crystalline to inverted hexagonal (Lalpha/H(II)) phase transitions of a number of phosphatidylethanolamines (PEs) and diacyl-alpha-D-glucosyl-sn-glycerols (alpha-D-GlcDAGs) containing linear saturated, linear unsaturated, branched or alicyclic hydrocarbon chains of various lengths were examined by differential scanning calorimetry and low-angle X-ray diffraction. As reported previously, for each homologous series of PEs or alpha-D-GlcDAGs, the Lbeta/Lalpha phase transition temperatures (Tm) increase and the Lalpha/H(II) phase transition temperatures (Th) decrease with increases in hydrocarbon chain length. The Tm and the especially the Th values for the PEs are higher than those of the corresponding alpha-D-GlcDAGs. For PEs having the same effective hydrocarbon chain length but different chain configurations, the Tm and Th values vary markedly but with an almost constant temperature interval (deltaT(L...

Biochemical Journal

Glucocerebrosidase, the lysosomal enzyme that is deficient in patients with Gaucher's disease... more Glucocerebrosidase, the lysosomal enzyme that is deficient in patients with Gaucher's disease, hydrolyses non-physiological aryl beta-D-glucosides and glucocerebroside, its substrate in vivo. We document that 2,3,-di-O-tetradecyl-1-O-(beta-D-glucopyranosyl)-sn-glycerol (2,3,-di-14:0-beta-Glc-DAG) inhibits human placental glucocerebrosidase activity in vitro (Ki 0.18 mM), and the nature of inhibition is typical of a mixed-type pattern. Furthermore, 2,3-di-14:0-beta-Glc-DAG was shown to be an excellent substrate for the lysosomal beta-glucosidase (Km 0.15 mM; Vmax. 19.8 units/mg) when compared with the natural substrate glucocerebroside (Km 0.080 mM; Vmax. 10.4 units/mg). The observations that (i) glucocerebrosidase-catalysed hydrolysis of 2,3-di-14:0-beta-Glc-DAG is inhibited by conduritol B epoxide and glucosylsphingosine, and (ii) spleen and brain extracts from patients with Gaucher's disease are unable to hydrolyse 2,3-di-14:O-beta-Glc-DAG demonstrate that the same active ...

Journal de Physique II, 1992

... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic ph... more ... Classification Physics Abstracts 61.30E 64.70&f Structural study of the inverted cubic phases of di-dodecyl alkyl-pD-glucopyranosyl-rac-glycerol David C. Turner (~>*) Zhen-Gang Wang (2), Sol M. Gruner (~), David A. Mannock (~) and Ronald N. McElhaney (3) * ...

Current Topics in Membranes, 1997

Molecular Crystals and Liquid Crystals, 2003

We have used X-ray diffraction and differential scanning calorimetry (DSC) to study the structure... more We have used X-ray diffraction and differential scanning calorimetry (DSC) to study the structure and lyotropic phase behaviour of two synthetic dialkyl glycolipids having β-D-glucose and β-D-galactose headgroups and two saturated tetradecyl (C14) chains. The diastereomeric compounds, 1,2-di-O-tetradecyl-3-O-(β-D-glucopyranosyl)-sn-glycerol (di-14:0–β-D-GlcDAG) and 1,2-di-O-tetradecyl-3-O-(β-D-galactopyranosyl)-sn-glycerol (di-14:0-β-D-GalDAG) show striking differences in their phase behaviour, particularly in the ordered lamellar phase region. Both compounds adopt the fluid lamellar Lα phase upon cooling from the HII phase, but below the chain-melting transition,di-14:0-β-D-GlcDAG forms a metastable Lβ gel phase, whereas di-14:0–β-D-GalDAG forms only crystalline lamellar phases, on the timescale of our measurements. We have determined the limiting hydrations of the various phases, and compare the findings from these glycolipids with those from our previous studies of the phospholipid didodecyl phosphatidylethanolamine (di-12:0-PE).

Langmuir, 1997

ABSTRACT We report on the effects of hydrostatic pressure and temperature on the phase and struct... more ABSTRACT We report on the effects of hydrostatic pressure and temperature on the phase and structural behavior of the complete range of the known, excess water, inverse lyotropic mesophases. This range of interfacial topologies is exhibited by homologous series of saturated C12, C14, and C16 dialkyl phosphatidylethanolamines (PE) and saturated C12 and C16 dialkyl xylopyranosylglycerols (xylolipids) in the p−T region 0−2.5 kbar and 30−130 °C. The PEs cover the mesophases with gentle interfacial curvature while the xylolipids cover the more curved mesophases. We demonstrate that temperature and pressure have noncongruent effects on the structural and the phase behavior. Quantitatively, mesophase lattice parameters and phase boundaries show small but observable differences in their functional dependence on pressure and temperature. Qualitatively, increasing pressure stabilizes inverse bicontinuous cubic phases in C14 PE. At atmospheric pressure only the C12 PE contains such phases. Conversely we find that increasing pressure destabilizes the inverse micellar cubic phase observed in the C16 xylolipid. In general a trend is seen for a stronger pressure effect in eliminating phases with larger packing costs, which we infer is due to differences in the effects of pressure and temperature on the monolayer's spontaneous mean curvature and its bending rigidity.

Chemistry and Physics of Lipids, 2002

The large intrinsic membrane dipole potential, b d , is important for protein insertion and funct... more The large intrinsic membrane dipole potential, b d , is important for protein insertion and functioning as well as for ion transport across natural and model membranes. However, the origin of b d is controversial. From experiments carried out with lipid monolayers, a significant dependence on the fatty acid chain length is suggested, whereas in experiments with lipid bilayers, the contribution of additional CH 2 -groups seems negligibly small compared with that of the phospholipid carbonyl groups and lipid-bound water molecules. To compare the impact of the CH 2 -groups of dipalmitoylphosphatidylcholine (DPPC) near and far from the glycerol backbone, we have varied the structure of DPPC by incorporation of sulfur atoms in place of methylene groups in different positions of the fatty acid chain. The b d of symmetric lipid bilayers containing one heteroatom was obtained from the charge relaxation of oppositely charged hydrophobic ions. We have found that the substitution for a S-atom of a CH 2 -group decreases b d . The effect (Db d = −22.6 mV) is most pronounced for S-atoms near the lipid head group while a S-atom substitution in the C 13 -or C 14 -position of the hydrocarbon chain does not effect the bilayer dipole potential. Most probably Db d does not originate from an altered dipole potential of the acyl chain containing an heteroatom but is mediated by the disruption of chain packing, leading to a decreased density of lipid dipoles in the membrane. : S 0 0 0 9 -3 0 8 4 ( 0 2 ) 0 0 0 1 3 -0 U. Peterson et al. /

Chemistry and Physics of Lipids, 2010

This review deals with the effect of variations in phospholipid and sterol structure on the natur... more This review deals with the effect of variations in phospholipid and sterol structure on the nature and magnitude of lipid-sterol interactions in lipid bilayer model membranes. The first portion of the review covers the effect of Chol itself on the thermotropic phase behavior and organization of a variety of different glycero-and sphingolipid membrane lipid classes, varying in the structure and charge of their polar headgroups and in the length and structure of their fatty acyl chains. The second part of this review deals with the effect of variations in sterol structure on the thermotropic phase behavior and organization primarily of the well studied DPPC model membrane system. In the third section, we focus on some of the contributions of sterol functional group chemistry, molecular conformation and dynamics, to sterollipid interactions. Using those studies, we re-examine the results of recently published experimental and computer-modeling studies to provide a new more dynamic molecular interpretation of sterol-lipid interactions. We suggest that the established view of the rigid sterol ring system and extended alkyl side-chain obtained from physical studies of cholesterol-phospholipid mixtures may not apply in lipid mixtures differing in their sterol chemical structure. L is lauroyl, M is myristoyl, P is palmitoyl, S is stearoyl, A is arachidoyl, E is elaidoyl and O is oleoyl (DMPC is dimyristoylphosphatidylcholine, etc.); LC , lamellar crystalline phase with tilted hydrocarbon chains; L ␤ or L ␤ , planar lamellar gel state with tilted or untilted hydrocarbon chains, respectively; P ␤ , rippled gel state with titled hydrocarbon chains; L␣, lamellar liquid-crystalline state; Lo or L d , lamellar liquid-ordered or liquid-disordered state, respectively; Tp and Tm, the pretransition and main phase transition temperature, respectively; Hp and Hm, enthalpy of the pretransition and main phase transition, respectively; T 1/2 , width of the DSC endotherm at half height ( • C), which is inversely related to the cooperativity of the phase transition; Tm shp , phase transition temperature of the sharp component of the DSC endotherm corresponding to the sterol-poor bilayer regions; Tm brd , phase transition temperature of the broad component of the DSC endotherm corresponding to the sterol-rich bilayer regions; Hm shp , phase transition enthalpy of the sharp component of the DSC endotherm corresponding to the sterol-poor bilayer regions; Hm brd , phase transition enthalpy of the broad component of the DSC endotherm corresponding to the sterol-rich bilayer regions; DSC, differential scanning calorimetry; FTIR, Fourier transform infrared; NMR, nuclear magnetic resonance.

Chemistry and Physics of Lipids, 2007

The thermotropic phase behaviour of aqueous dispersions of some synthetic 1,2-di-O-alkyl-3-O-(␤-d... more The thermotropic phase behaviour of aqueous dispersions of some synthetic 1,2-di-O-alkyl-3-O-(␤-d-galactosyl)-rac-glycerols (rac-␤-d-GalDAGs) with both odd and even hydrocarbon chain lengths was studied by differential scanning calorimetry (DSC), small-angle (SAXS) and wide-angle (WAXS) X-ray diffraction. DSC heating curves show a complex pattern of lamellar (L) and nonlamellar (NL) phase polymorphism dependent on the sample's thermal history. On cooling from 95 • C and immediate reheating, rac-␤-d-GalDAGs typically show a single, strongly energetic phase transition, corresponding to either a lamellar gel/liquid-crystalline (L ␤ /L ␣ ) phase transition (N ≤ 15 carbon atoms) or a lamellar gel/inverted hexagonal (L ␤ /H II ) phase transition (N ≥ 16). At higher temperatures, some shorter chain compounds (N = 10-13) exhibit additional endothermic phase transitions, identified as L/NL phase transitions using SAXS/WAXS. The NL morphology and the number of associated intermediate transitions vary with hydrocarbon chain length. Typically, at temperatures just above the L ␣ phase boundary, a region of phase coexistence consisting of two inverted cubic (Q II ) phases are observed. The space group of the cubic phase seen on initial heating has not been determined; however, on further heating, this Q II phase disappears, enabling the identification of the second Q II phase as Pn3m (space group Q 224 ). Only the Pn3m phase is seen on cooling.

Chemistry and Physics of Lipids, 2011

Epicoprostanol Phosphatidylcholine Sterol-lipid interactions Phospholipid thermotropic phase beha... more Epicoprostanol Phosphatidylcholine Sterol-lipid interactions Phospholipid thermotropic phase behaviour Differential scanning calorimetry a b s t r a c t