Effects of (R)- and (S)-α-Hydroxylation of Acyl Chains in Sphingosine,Dihydrosphingosine, and Phytosphingosine Ceramides on Phase Behavior and Permeability of Skin Lipid Models

Ceramides (Cers) with α-hydroxylated acyl chains comprise about a third of all extractable skin Cers and are required for permeability barrier homeostasis. We have probed here the effects of Cer hydroxylation on their behavior in lipid models comprising the major SC lipids, Cer/free fatty acids (C ₁₆-C ₂₄)/cholesterol, and a minor component, cholesteryl sulfate. Namely, Cers with (R)-α-hydroxy lignoceroyl chains attached to sphingosine (Cer AS), dihydrosphingosine (Cer AdS), and phytosphingosine (Cer AP) were compared to their unnatural (S)-diastereomers and to Cers with non-hydroxylated lignoceroyl chains attached to sphingosine (Cer NS), dihydrosphingosine (Cer NdS), and phytosphingosine (Cer NP). By comparing several biophysical parameters (lamellar organization by X-ray diffraction, chain order, lateral packing, phase transitions, and lipid mixing by infrared spectroscopy using deuterated lipids) and the permeabilities of these models (water loss and two permeability markers), we conclude that there is no general or common consequence of Cer α-hydroxylation. Instead, we found a rich mix of effects, highly dependent on the sphingoid base chain, configuration at the α-carbon, and permeability marker used. We found that the model membranes with unnatural Cer (S)-AS have fewer orthorhombically packed lipid chains than those based on the (R)-diastereomer. In addition, physiological (R)-configuration decreases the permeability of membranes, with Cer (R)-AdS to theophylline, and increases the lipid chain order in model systems with natural Cer (R)-AP. Thus, each Cer subclass makes a distinct contribution to the structural organization and function of the skin lipid barrier.     

Physicochemical analysis of liposome membranes consisting of model lipids in the stratum corneum

Lamellar lipid layers in the stratum corneum (SC), the outermost layer of the skin, act as a primary permeability barrier to protect the body. The roles of SC lipid composition and membrane structure in skin barrier function have been extensively investigated using ex-vivo SC samples and reconstructed SC lipids in the form of multi-lamellar lipids or liposomes. The primary lipids, especially ceramide, have been found to be highly important. Atopic dermatitis (AD) is a well-known chronic inflammatory skin disease with immunologic and epidermal abnormalities of the permeability barrier; therefore, a comparison of SC lipids in AD skin with those in normal skin is a promising method to explore the mechanisms of skin barrier function. Here, we focused on the effect of sphingoids (ceramide metabolites and a minor component of the SC lipids) and their content/species on skin barrier function. A significant difference in the leakage ratio was observed between model SC lipid liposomes with a different sphingolipid ratio (sphingosine/sphinganine), with a value of 5.43 for normal skin vs. 14.3 for AD skin. This result shows a good concordance with AD mouse experiments. Therefore, an alteration in the composition of minor SC lipids resulting from a ceramide metabolic abnormality can affect the membrane integrity (i.e., skin barrier function). Small angle X-ray scattering (SAXS) measurements revealed no distinct differences in the SAXS pattern between the 3 models, with all models forming a rigid membrane (i.e., a nearly hydrated solid). According to increasing the temperature, the peaks indicated that the lamellar structures decreased in all models and that the lateral packing of lipids decreased, which suggested annealing or melting of the gel to a liquid crystal, although no distinct phase transition was observed through fluorescence anisotropy measurements. Hence, we assume that the altered sphingoid composition triggers local membrane structural changes (i.e., formation of domains or clusters).     

Computer simulation on the self-assembly of associating polymers

We present the results of Monte Carlo simulations of self-assembly in melt of pseudo-block copolymer formed through the association of associating polymer chains with attractive end-groups (sticker sites). Complexities of the phase structures result from these pseudo-block copolymers strongly depend on parameters, such as attractive interaction strength between two stickers and chain length of associating polymers. The weak, intermediate and strong interactions between two stickers lead, respectively, to the macro-separated, disordered and ordered lamellar phase structures. The ordered lamellar phases formed by these pseudo-block copolymers are more stable than that formed by pure diblock copolymers. Pseudo-block copolymers with shorter associating polymer chain prefer to form ordered lamellar phase and that with longer associating chain tend to form disordered phase.     

Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin

Inactive cortisone is converted into active cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Excessive levels of active glucocorticoids could deteriorate skin barrier function; barrier impairment is also observed in aged skin. In this study, we aimed to determine whether permeability barrier impairment in the aged skin could be related to increased 11β-HSD1 expression. Aged humans (n = 10) showed increased cortisol in the stratum corneum (SC) and oral epithelium, compared to young subjects (n = 10). 11β-HSD1 expression (as assessed via immunohistochemical staining) was higher in the aged murine skin. Aged hairless mice (56-week-old, n = 5) manifested greater transepidermal water loss, lower SC hydration, and higher levels of serum inflammatory cytokines than the young mice (8-week-old, n = 5). Aged 11β-HSD1 knockout mice (n = 11), 11β-HSD1 inhibitor (INHI)-treated aged wild type (WT) mice (n = 5) and young WT mice (n = 10) exhibited reduced SC corticosterone level. Corneodesmosome density was low in WT aged mice (n = 5), but high in aged 11β-HSD1 knockout and aged INHI-treated WT mice. Aged mice exhibited lower SC lipid levels; this effect was reversed by INHI treatment. Therefore, upregulation of 11β-HSD1 in the aged skin increases the active-glucocorticoid levels; this suppresses SC lipid biosynthesis, leading to impaired epidermal permeability barrier.     

Liquid crystalline polysurfactant

Summary A new kind of amphiphilic polymer (PAMC₁₆S) has been synthesized where the amphiphilic moiety is attached as a side chain via the hydrophilic end to the polymer backbone. DSC, POM, and WAXD study revealed that the polysurfactant formed thermotropic liquid crystalline phase. The liquid crystalline domains appeared after annealed at the melt for a period of time, and evolved with annealing. It was indicated that the thermodynamic effect played a significant role on the self—aggregation of hydrophobic ends, so as to form liquid crystalline structure. X—ray investigation suggested that the mesophase structure could be described as smectic with lamellar type of packing, in which alkyl tails aggregated to form layer. A model of supermolecular structure was given.     

On permanent cilia and segregation in the crystallization of binary blends of monodisperse n-alkanes

The isothermal crystallization kinetics and morphology have been investigated for a series of dilute binary blends using six monodisperse n-alkanes as guest in C₁₆₂H₃₂₆ as host. Two patterns of behaviour were observed. Guest molecules shorter than the host segregate as a separate population causing growth rates to become both reduced and non-linear. Morphologies are then noticeably less spherulitic than the host with less divergence between adjacent dominant lamellae but exhibiting no additional splaying at zero supercooling. By contrast, those blends with an n-alkane longer than the host co-crystallize (producing permanent cilia of controlled length) with a constant, but reduced, isothermal lamellar growth rate. Textures are now more spherulitic than the host, with additional splaying of an amount directly proportional to the number of permanent cilia and increasing with their length. The intercepts and slopes of plots of splaying data against supercooling are consistently related to permanent cilia plus inclined packing of initially rough lamellar surfaces and transient ciliation, respectively. The underlying causes of spherulitic growth for long molecules are thereby further confirmed and clarified.     

Solubilization of model stratum corneum liposomes by quaternary ammonium surfactants

The solubilizing interactions of a series of quaternary ammonium surfactants [alkyl chain lengths C-12 (DoTAB), C-14 (TeTAB), and C-16 (HeTAB)] with liposomes formed by a mixture of lipids modeling the stratum corneum (SC) lipid composition (40% ceramides, 25% cholesterol, 25% palmitic acid, and 10% of cholesteryl sulfate) were investigated. Surfactant/lipid molar ratios (Re) and bilayer/aqueous phase partition coefficients (K) were determined by monitoring changes in static light scattering of the system during solubilization. Free surfactant concentration was always similar to the critical micelle concentration (CMC). A general assumption for phosphatidylcholine (PC) liposomes suggests that the free surfactant concentration must reach CMC for solubilization to occur. This assumption can be applied to SC liposomes in this study, and indicates that liposome solubilization was mainly driven by mixed micelle formation. The Re and K parameters fell as the surfactant alkyl chain length decreased or CMC increased. Thus, a higher CMC corrsponds to an increased ability of these surfactants to saturate or solubilize SC liposomes and to a lower degree of partitioning into liposomes or affinity with these bilayer structures. The overall balance of these opposing tendencies shows that TeTAB had the highest effectiveness with respect to the saturation and solubilization of SC structures in terms of total surfactant needed to produce these effects. Different trends in surfactant interaction with SC liposomes were observed when comparing Re and K parameters with those for PC liposomes. Because SC liposomes were more resistant to the surfactant action, the affinity of surfactants with these bilayer structures was higher in all cases.     

Ternary Phase Diagram of β-Sitosterol–γ-Oryzanol–Canola Oil

β-Sitosterol and γ-oryzanol have been shown to form unique structures in canola oil that have the potential to act as saturated and trans fat replacers [1–7]. The ternary phase, reported herein, illustrates numerous interesting physical systems. At high canola oil ratios with low β-sitosterol and γ-oryzanol concentrations, the system has a crystal structure capable of mimicking fat crystal networks. Four mesophases are identified based on Bragg’s ratios using small angle X-ray scattering. Two mesophases are lamellar crystals, one is the cubic P phase, and the fourth is an amorphous material due to the low solids content. Wide-angle X-ray further subcategorized the phases based on polymorphic divisions of the hydrocarbon side chain packing. In all, six distinct phases are reported, ranging from lamellar crystals, to liquid crystals to what appears to be a lipid glass.     

Rapid colorimetric determination of free fatty acids

In 1964, a method was described for the determination of free fatty acids (FFAs) in vegetable oil. This paper describes an expansion of that work, improving the sensitivity and reproducibility of the method, as well as examination of solubilities of the copper soaps as a function of chain length and unsaturation. Involvement of the micellar structure was reviewed. Finally, a procedure is described that permits very rapid determination of FFA at the 2.0–14.0 μmol (0.5–4.0 mg oleic acid) level, and the results with several oils are given. Particular attention was given to evaluation of solvent systems which would extract the copper complexes. Presented in part at the AOCS Meeting in San Francisco, April 1969. Technical Paper No. 4036, Oregon Agricultural Experiment Station.     

Morphologies of diblock copolymer confined in a slit with patterned surfaces studied by dissipative particle dynamics

Diblock copolymers with ordered mesophase structures have been used as templates for nano-fabrication. Unfortunately, the ordered structure only exists at micromete rscale areas, which precludes its use in many advanced applications. To overcome this disadvantage, the diblock copolymer confined in a restricted system with a patterned surface is proved to be an effective means to prohibit the formation of defects and obtain perfect ordered domains. In this work, the morphologies of a thin film of diblock copolymer confined between patterned and neutral surfaces were studied by dissipative particle dynamics. It is shown that the morphology of the symmetric diblock copolymer is affected by the ratio of the pattern period on the surface to the lamellar period of the symmetric diblock copolymer and by the repulsion parameters between blocks and wall particles. To eliminate the defects in the lamellar phase, the pattern period on the surface must match the lamellar period. The difference in the interface energy of different compartments of the pattern should increase with increasing film thickness. The pattern period on the surface has a scaling relationship with the chain length, which is the same as that between the lamellar period and the chain length. The lamellar period is also affected by the polydispersity of the symmetric diblock copolymer. The total period is the average of the period of each component multiplied by the weight of its volume ratio. The morphologies of asymmetric diblock copolymers are also affected by the pattern on the surface, especially when the matching period of the asymmetric diblock copolymer is equal to the pattern period, which is approximately equal to the lamellar period of a symmetric diblock copolymer with the same chain length.     

Determination of Free Fatty Acids in Edible Oils with the Use of a Variable Filter Array IR Spectrometer

The feasibility of employing a portable variable filter array (VFA) IR spectrometer equipped with a transmission flow cell to quantitatively analyze edible oils or biodiesel feedstocks for free fatty acids (FFA) was evaluated. The approach to FFA determination employed was based on a previously reported FTIR method that involves the extraction of FFAs into methanol containing the base NaHNCN, which converts the FFAs to their salts, followed by measurement of the carboxylate absorbance at ~1,573 cm⁻¹ in the spectrum of the methanol phase. When this methodology was implemented on the low-resolution VFA-IR spectrometer, the analytical performance was comparable to that of conventional FTIR instrumentation at FFA concentrations of <1%. However, at higher FFA levels, the relatively weak pulsed IR source of the VFA-IR spectrometer was found to provide insufficient energy for accurate measurement of the carboxylate absorption superimposed on the strong methanol absorption at ~1,450 cm⁻¹. By changing the extraction solvent to ethanol (EtOH), good spectra and calibrations could be obtained over an FFA range of 0–5%, having an overall SD of ±0.07% FFA. Based on this assessment, a VFA-IR spectrometer provides an economical instrumental means for at-line monitoring of FFA levels in crude and refined edible oils and biodiesel feedstocks, capable of analyzing ~20–30 prepared samples per hour.     

Self‐Aggregation and Emulsifying Properties of Methyl Ester Sulfonate Surfactants

Methyl ester sulfonate (MES) anionic surfactants made from natural resources are of particular interest as sustainable surfactants. They offer good physicochemical properties for applications as detergents and emulsifiers. The liquid crystal structures of MES surfactants synthesized in a previous work were determined by polarizing optical microscopy (POM) and small‐angle X‐ray scattering (SAXS). The emulsifying activity for each surfactant was also measured, and the stability of emulsions was estimated and compared to that induced by sodium dodecyl sulfate (SDS). The POM micrographs showed the presence of birefringent textures. Several factors, including temperature and hydration, influenced the stability of the phases and their structure. SAXS confirmed the structure of the phases formed by dry and hydrated ф‐MES surfactants at 25 °C, giving the position of peaks corresponding to the ratio 1:2:3 and revealing the phase transitions of lamellar to double lamellar or the reverse. Also, the Bragg distance (d) decreased with an increase in chain length from 13 to 17 carbon atoms and an increase in the area per molecule of surfactant. The geometric packing parameters were also determined, and suggest that surfactants are tilted. The stability of surfactant emulsions is around 60%, which is comparable to that of SDS. The micrographs show that the emulsions formed are O/W, and an increase in chain length gives rise to a decrease in the size of the emulsion droplets. These results are confirmed by the values of hydrophilic‐lipophilic balance (HLB) which reveals the hydrophilic nature of these surfactants.     

Thermotropic liquid-crystalline polyesters and polyesteramides

Thermotropic behaviour is observed in a number of aromatic polyesteramides containing p-phenylene or substituted p-phenylene groups. In such polymers, a substantial proportion of co-polymerised units lacking rigid rod structure can be tolerated without loss of thermotropic behaviour. Anisotropic melts can be formed at very short average chain length. The upper temperature limit of stability of the anisotropic phase is lower the shorter the average chain length and the greater the proportion of relatively flexible units. Some polyesteramides formally derived from p-N-methylaminophenol also exhibit thermotropic behaviour.     

Bile Acid Signaling in Inflammatory Bowel Disease

Inflammatory bowel disease is a chronic, idiopathic and complex condition, which most often manifests itself in the form of ulcerative colitis or Crohn’s disease. Both forms are associated with dysregulation of the mucosal immune system, compromised intestinal epithelial barrier, and dysbiosis of the gut microbiome. It has been observed for a long time that bile acids are involved in inflammatory disorders, and recent studies show their significant physiological role, reaching far beyond being emulsifiers helping in digestion of lipids. Bile acids are also signaling molecules, which act, among other things, on lipid metabolism and immune responses, through several nuclear and membrane receptors in hepatocytes, enterocytes and cells of the immune system. Gut microbiota homeostasis also seems to be affected, directly and indirectly, by bile acid metabolism and signaling. This review summarizes recent advances in the field of bile acid signaling, studies of inflamed gut microbiome, and the therapeutic potential of bile acids in the context of inflammatory bowel disease.     

Influence of compositional gradient on the phase behavior of ternary symmetric homopolymer-copolymer blends: A Monte Carlo study

The formation of bicontinuous microemulsions (BUEs) in ternary symmetric blends including two immiscible homopolymers A and B as well as a linear gradient copolymer G is verified by Monte Carlo simulations. Four phase diagrams as a function of segregation strength and blend composition are constructed to show the effects of compositional gradient. Compared with the blends of A/B/diblock copolymers, the BUE phase occupies a broader region in the phase diagram of the A/B/G blends and is replaced by the three-phase coexistence phases of A + B + L or A + B + D at a much lower chain length ratio. Moreover, the lamellar phase is formed at a higher value of segregation strength, has a shorter periodic length and lower orientational order, and spans a narrower range of the phase diagram. A “counteraction effect” is proposed to explain those discrepancies caused by gradient copolymers.     

Phase diagram of α-sulfonate methyl esters derived from palm stearin/alcohol/water systems

Phase diagrams of α-sulfonate methyl ester derived from palm stearin (α-SMEPS)/alcohol/water systems were mapped at 30±0.1°C. Two main regions—an isotropic and a lamellar liquid crystalline—were the focal points in this system. An increase in alcohol chain length decreased the isotropic region and increased the lamellar liquid crystal region. In the isotropic region, self-assembly of α-SMEPS at different alcohol chain lengths was determined by using conductivity and viscosity measurements. The phase boundaries of micelle to bicontinuous structure and bicontinuous structure to inverse micelle transitions in the isotropic regions are proposed from these analytical methods. The increase in alcohol chain length shifted the micelle ⇆ bicontinuous structure to the water-rich corner, and the bicontinuous structure ⇆ inverse micelle transition moved toward the alcohol-rich corner.     

Effects of Concentrations on the Transdermal Permeation Enhancing Mechanisms of Borneol: A Coarse-Grained Molecular Dynamics Simulation on Mixed-Bilayer Membranes

Borneol is a natural permeation enhancer that is effective in drugs used in traditional clinical practices as well as in modern scientific research. However, its molecular mechanism is not fully understood. In this study, a mixed coarse-grained model of stratum corneum (SC) lipid bilayer comprised of Ceramide-N-sphingosine (CER NS) 24:0, cholesterol (CHOL) and free fatty acids (FFA) 24:0 (2:2:1) was used to examine the permeation enhancing mechanism of borneol on the model drug osthole. We found two different mechanisms that were dependent on concentrations levels of borneol. At low concentrations, the lipid system maintained a bilayer structure. The addition of borneol made the lipid bilayer loosen and improved drug permeation. The “pull” effect of borneol also improved drug permeation. However, for a strongly hydrophobic drug like osthole, the permeation enhancement of borneol was limited. When most borneol molecules permeated into bilayers and were located at the hydrophobic tail region, the spatial competition effect inhibited drug molecules from permeating deeper into the bilayer. At high concentrations, borneol led to the formation of water pores and long-lived reversed micelles. This improved the permeation of osthole and possibly other hydrophobic or hydrophilic drugs through the SC. Our simulation results were supported by Franz diffusion tests and transmission electron microscope (TEM) experiments.     

Urea-based fractionation of seed oil samples containing fatty acids and acylglycerols of polyunsaturated and hydroxy fatty acids

The selectivity and efficiency of urea complex (UC) formation-based fractionation of free fatty acids (FFA) were examined. A rapid, simple, and inexpensive procedure recently developed for urea fractionation was applied to lipid mixtures containing various polyunsaturated and hydroxy FFA species. Urea treatment proved useful for isolating polyunsaturated FFA (PUFA) from FFA derived from fish, borage, and linseed oils by removal of saturated and monounsaturated FFA, but was not effective for isolating hydroxy FFA from the FFA derived from castor, Lesquerella, and Dimorphotheca oils. In situations where FFA within the crystalline or UC phase were rich in PUFA, the urea/FFA mole ratio of the UC was relatively higher, with lower recovery of FFA in this phase. The distribution of urea between the crystalline phase and the solvent was not significantly affected by the FFA composition of feed nor the overall ratio of FFA to urea. It was strongly dependent on the overall mass fraction of solvent. Phospholipids and mono-, di-, and triacylglycerols were poor templates for UC formation relative to FFA. Their inclusion in acylglycerol mixtures containing FFA reduced UC formation.     

Fatty acid composition of adultSchistosoma mansoni

The fatty acid composition of triglyceride and total phospholipid fractions of adultSchistosoma mansoni has been examined. Both triglyceride and phospholipid contained fatty acids varying in chain length from 12 through 24 carbons; trace amounts of shorter chain components were found in the triglyceride fraction. A docosahexaenoic acid in the triglyceride fraction represented the highest degree of unsaturation encountered. Branched chain fatty acids of 16 and 18 carbons were found in both phospholipid and triglyceride. Examination of fatty acids from fluke total lipid revealed the presence of small amounts of odd numbered carbon fatty acids varying in chain length from 13 through 23 carbons.     

Diffusional and orientational dynamics of various single terylene diimide conjugates in mesoporous materials

Mesoporous silica materials are ideally suited as host–guest systems in nanoscience with applications ranging from molecular sieves, catalysts, nanosensors to drug-delivery-systems. For all these applications a thorough understanding of the interactions between the mesoporous host system and the guest molecules is vital. Here, we investigate these interactions using single molecule spectroscopy (SMS) to study the dynamics of three different terylene diimide (TDI) dyes acting as molecular probes in hexagonal and lamellar mesoporous silica films. The diffusion behaviour in the hexagonal phase is represented by the trajectories of the single molecules. These trajectories are highly structured and thus provide information about the underlying host structure, such as domain size or the presence of defects inside the host structure. The three structurally different TDI derivatives allowed studying the influence of the molecular structure of the guest on the translational diffusion behaviour in the hexagonal phase and the lamellar phase. In the lamellar phase, the differences between the three guests are quite dramatic. First, two populations of diffusing molecules – one with parallel orientation of the molecules to the lamellae and the other with perpendicular orientation – could be observed for two of the TDI derivatives. These populations differ drastically in their translational diffusion behaviour. Depending on the TDI derivative, the ratio between the two populations is different. Additionally, switching between the two populations was observed. These data provide new insights into host–guest interactions like the influence of the molecular structure of the guest molecules on their diffusional as well as on their orientational behaviour in structurally confined guest systems.