Thermotropic Phase Behavior Research Articles

Self-Assembly of Ionic Superdiscs in Nanopores.

Discotic ionic liquid crystals (DILCs) consist of self-assembled superdiscs of cations and anions that spontaneously stack in linear columns with high one-dimensional ionic and electronic charge mobility, making them prominent model systems for functional soft matter. Compared to classical nonionic discotic liquid crystals, many liquid crystalline structures with a combination of electronic and ionic conductivity have been reported, which are of interest for separation membranes, artificial ion/proton conducting membranes, and optoelectronics. Unfortunately, a homogeneous alignment of the DILCs on the macroscale is often not achievable, which significantly limits the applicability of DILCs. Infiltration into nanoporous solid scaffolds can, in principle, overcome this drawback. However, due to the experimental challenges to scrutinize liquid crystalline order in extreme spatial confinement, little is known about the structures of DILCs in nanopores. Here, we present temperature-dependent high-resolution optical birefringence measurement and 3D reciprocal space mapping based on synchrotron X-ray scattering to investigate the thermotropic phase behavior of dopamine-based ionic liquid crystals confined in cylindrical channels of 180 nm diameter in macroscopic anodic aluminum oxide membranes. As a function of the membranes' hydrophilicity and thus the molecular anchoring to the pore walls (edge-on or face-on) and the variation of the hydrophilic-hydrophobic balance between the aromatic cores and the alkyl side chain motifs of the superdiscs by tailored chemical synthesis, we find a particularly rich phase behavior, which is not present in the bulk state. It is governed by a complex interplay of liquid crystalline elastic energies (bending and splay deformations), polar interactions, and pure geometric confinement and includes textural transitions between radial and axial alignment of the columns with respect to the long nanochannel axis. Furthermore, confinement-induced continuous order formation is observed in contrast to discontinuous first-order phase transitions, which can be quantitatively described by Landau-de Gennes free energy models for liquid crystalline order transitions in confinement. Our observations suggest that the infiltration of DILCs into nanoporous solids allows tailoring their nanoscale texture and ion channel formation and thus their electrical and optical functionalities over an even wider range than in the bulk state in a homogeneous manner on the centimeter scale as controlled by the monolithic nanoporous scaffolds.

Limited miscibility in hydrated DPPC – Lyso-PPC systems

Hydrated dipalmitoylphosphatidylcholine (DPPC) and lyso-palmitoylphosphatidylcholine (Lyso-PPC, abbreviated as LPC) mixtures form vesicles composed from periodically or randomly arranged layers and micelle-like nanoparticles, as revealed by a wide range of thermodynamical, structural, and morphological characterization methods. Based on five different experimental methods, we have reconstructed the phase diagram of the system. The micelle-like objects are strongly anisotropic and are identified as bicelles. Even a small amount of LPC induces drastic changes in the thermotropic phase behaviour of DPPC. Here, an interdigitated gel (LβI) structure, coexisting with the other gel phases, forms at moderate LPC concentration. Bicelles and LβI structured vesicles appear in the equimolar LPC ratio range (0.4 ≤ XLPC ≤ 0.6). Two complex phase transition regimes are detectable. Between 36–40 °C, bicelles are pre-melted while domains of LβI structure are “crystallized” through local endothermic and exothermic transitions, respectively. Then, around 42 °C the chains of both the LβI and bicelles melt completely. Above the equimolar LPC ratio range (XLPC > 0.6) the chain melting in the LβI structure vanishes, while this transition still exists in the chain region of bicelles. This wealth of structural forms, due to the weak first order transition characteristics, is highly sensitive for perturbations and interactions induced by e.g. the presence of membrane proteins.

Structure, Self-Assembly, and Phase Behavior of Neuroactive N-Acyl GABAs: Doxorubicin Encapsulation in NPGABA/DPPC Liposomes and Release Studies.

N-Acylated amino acids and neurotransmitters in mammals exert significant biological effects on the nervous system, immune responses, and vasculature. N-Acyl derivatives of γ-aminobutyric acid (N-acyl GABA), which belong to both classes mentioned above, are prominent among them. In this work, a homologous series of N-acyl GABAs bearing saturated N-acyl chains (C8-C18) have been synthesized and characterized with respect to self-assembly, thermotropic phase behavior, and supramolecular organization. Differential scanning calorimetric studies revealed that the transition enthalpies and entropies of N-acyl GABAs are linearly dependent on the acyl chain length. The crystal structure of N-tridecanoyl GABA showed that the molecules are packed in bilayers with the acyl chains aligned parallel to the bilayer normal and that the carboxyl groups from opposite layers associate to form dimeric structures involving strong O-H···O hydrogen bonds. In addition, N-H···O and C-H···O hydrogen bonds between amide moieties of adjacent molecules within each layer stabilize the molecular packing. Powder X-ray diffraction studies showed odd-even alternation in the d spacings, suggesting that the odd chain and even chain compounds pack differently. Equimolar mixtures of N-palmitoyl GABA and dipalmitoylphosphatidylcholine (DPPC) were found to form stable unilamellar vesicles with diameters of ∼300-340 nm, which could encapsulate doxorubicin, an anticancer drug, with higher efficiency and better release characteristics than DPPC liposomes at physiologically relevant pH. These liposomes exhibit faster release of doxorubicin at acidic pH (<7.0), indicating their potential utility as drug carriers in cancer chemotherapy.

Phase diagram of a rigid rod system with attractive end groups

We present a molecular dynamics study into the thermotropic liquid crystalline phase behaviour of a coarse-grained model of a rigid bolaamphiphilic molecule. The model consists of 11 spherical beads held in a fixed linear arrangement, where the two opposing terminal beads are self-attracting, mimicking hydrophilic segments and the remaining internal beads, as well as cross-bead interactions, are softly repulsive, mimicking hydrophobic organic segments. The effect of the model’s end bead self-attraction strength on liquid crystalline phase behaviour is studied. Coexistence points between the smectic A, nematic and isotropic phases exhibited by the model are determined following a thermodynamic integration pathway, using equations of state constructed by multiple histogram reweighting of simulation data. Variants of Gibbs–Duhem integration are used to trace pressure–temperature coexistence curves. Under isobaric conditions, the effect of increasing the end-group self-attraction on the nematic–isotropic coexistence temperature is relatively small; however, the nematic phase stability is reduced at the expense of a significant increase in the smectic A–nematic coexistence temperature. Lower temperature simulations show the approximate smectic A–crystalline transition temperature to be only weakly dependent on the strength of the end-group self-attraction.

The impact of palmitoyl glycyl-histidyl-lysine on phospholipid model membranes

BackgroundPalmitoyl glycyl-histidyl-lysine (Pal-GHK), a peptide amphiphile derived from the GHK tripeptide, has gained attention for its diverse bioactive properties and applications in skincare formulations. This study delves into the interactions and effects of Pal-GHK on phospholipid model membranes. Using a thin film hydration-sonication method, Pal-GHK and hydrogenated soy phosphatidylcholine (HSPC) were combined to create lipid vesicles. MethodsVarious analytical techniques, including dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), fluorescence polarization (FP), and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), were employed to comprehensively assess the impact of Pal-GHK on the lipid bilayer domain. Significant FindingsThe results reveal insights into the size, zeta potential, storage stability, morphology, thermotropic phase behavior, molecular arrangement, and lipid ordering within the HSPC membranes in the presence of Pal-GHK. The introduction of Pal-GHK increased vesicle size, surface charge density, and storage stability in HSPC-rich vesicles. The addition of Pal-GHK dominated the endothermic phase behavior of the lipid vesicles and increased the proportion of gauche conformation in the acyl chains of HSPC, inducing molecular fluidity in the hydrophobic region of the lipid membrane in its gel state. These findings contribute to our understanding of the interactions between Pal-GHK and lipid model membranes, holding significance for various scientific disciplines and potential applications.

Chameleonic amphiphile: The unique multiple self-assembly properties of a natural glycolipid in excess of water.

Chameleons are stunning reptiles which change colour according to the surrounding environment. In astrophysics, chameleons are particles whose mass varies in the surrounding matter. Here, we show the chameleonic self-assembly behavior of a low molecular weight (LMW) amphiphile, a broad class of molecules widely studied for several decades. Their ability to self-assemble in water make them both fascinating and useful compounds for a number of applications. Under thermodynamic conditions, their thermotropic and lyotropic phase behavior is generally predicted in relation to their molecular shape, as seen for classical head-tail molecules like surfactants or phospholipids. However, many exceptions do exist, either when amphiphiles have unconventional shapes, e.g., bolaform or gemini, or when they contain functional groups which undergo specific interactions such as H-bonding or π-π stacking. In excess water, surfactants form micelles, phospholipids form vesicles or lamellar phases, and functional amphiphiles often form micelles or fibers. Here, we show the multiphase behavior, much richer and more unpredictable than what it is known for most amphiphiles, of a biobased glycolipid produced by the yeast S. bombicola ΔugtB1. In excess water and within a narrow pH range around neutrality, this compound assembles into micelles, uni- and multilamellar vesicles, lamellae and fibers, simply as a function of changing pH, temperature and counterions. This rich phase behavior is not only interesting in itself, it also generates a number of diverse biocompatible and biodegradable soft self-assembled materials like hydrogels, complex coacervates and drug carriers.

Elucidating the nanostructure of small interfering RNA-loaded lipidoid-polymer hybrid nanoparticles

We analyzed the structural and material properties of small interfering RNA (siRNA)-loaded lipid-polymer hybrid nanoparticles (LPNs) containing ionizable lipidoid and poly(dl-lactic-co-glycolic acid) (PLGA) using small-angle X-ray scattering, cryogenic transmission electron microscopy, polarized light microscopy, the Langmuir monolayer methodology, differential scanning calorimetry, and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. Scattering analyses showed that bulk lipidoid self-assemble into lamellar structures with a d-spacing of 38 Å, whereas lipidoid-siRNA lipoplexes display an in-plane lateral organization of siRNA in between lipidoid bilayers with a repeat distance of approximately 55 Å. The siRNA-loaded LPNs adopted a core–shell structure with an interaxial alignment of siRNA between lipidoid shell bilayers. Langmuir monolayer experiments showed a distinct interaction between the lipidoid headgroups and siRNA, which was dependent on buffer subphase pH. Thermal analyses suggested that PLGA and lipidoid interact, which was evident from a shift in the phase transition temperature of lipidoid, and the thermotropic phase behavior of lipidoid was affected by inclusion of siRNA. ATR-FTIR data confirmed the shift or disappearance of characteristic absorption bands of siRNA after lipidoid binding. In conclusion, siRNA-loaded LPNs display a core–shell structure, wherein the polymeric core functions as a colloid matrix support for siRNA-loaded lipidoid shell layers.

Milk sphingosomes as lipid carriers for tocopherols in aqueous foods: Thermotropic phase behaviour and morphology

Foods containing polyunsaturated lipids are prone to oxidation. Designing food-grade hydrocolloidal encapsulation systems able to load lipophilic antioxidant molecules, such as tocopherols (vitamin E), is necessary to prevent oxidation and its deleterous consequences. In this study, we hypothesised that α-tocopherol molecules could incorporate in a host membrane composed of milk sphingomyelin (milk-SM) and performed a multi-scale biophysical study. The thermal properties of milk-SM bilayers with various molar proportions of α-tocopherol were characterised by differential scanning calorimetry (DSC), their structural properties were examined by X-ray diffraction (XRD). The miscibility between milk-SM and α-tocopherol was investigated in mixed Langmuir monolayers. The morphology of milk-SM sphingosomes was observed by confocal laser scanning microscopy (CLSM). We found that molecules of α-tocopherol inserted into the milk-SM bilayers and induced a physical desorganisation in the membrane packing, both in the ordered and fluid states. In the presence of α-tocopherol, the bilayers were no longer in a gel phase below the phase transition temperature Tm, but in the liquid ordered Lo phase. Furthermore, the sphingosomes formed elongated structures in presence of α-tocopherol as a result of membrane softening and changes in the bilayer curvature associated to membrane fusion. The findings of this work contribute in a better understanding of the capacity of milk-SM bilayers to incorporate guest molecules. Milk-SM sphingosomes loaded with tocopherols could be used to prevent oxidation in aqueous foods containing polyunsaturated lipids such as oil-in-water emulsions.

Staphylococcus aureus Carotenoids Modulate the Thermotropic Phase Behavior of Model Systems That Mimic Its Membrane Composition.

Staphylococcus aureus (S. aureus) is a pathogenic gram-positive bacterium that normally resides in the skin and nose of the human body. It is subject to fluctuations in environmental conditions that may affect the integrity of the membrane. S. aureus produces carotenoids, which act as antioxidants. However, these carotenoids have also been implicated in modulating the biophysical properties of the membrane. Here, we investigate how carotenoids modulate the thermotropic phase behavior of model systems that mimic the phospholipid composition of S. aureus. We found that carotenoids depress the main phase transition of DMPG and CL, indicating that they strongly affect cooperativity of membrane lipids in their gel phase. In addition, carotenoids modulate the phase behavior of mixtures of DMPG and CL, indicating that they may play a role in modulation of lipid domain formation in S. aureus membranes.

Nematic-to-Isotropic Phase Transition in Poly(L-Lactide) with Addition of Cyclodextrin during Abiotic Degradation Study.

Poly(L-lactide) is capable of self-assembly into a nematic mesophase under the influence of temperature and mechanical stresses. Therefore, subsequent poly(L-lactide) films were obtained and characterized, showing nematic liquid crystal properties both before and after degradation. Herein, we present that, by introducing β-cyclodextrin into the polymer matrix, it is possible to obtain a chiral nematic mesophase during pressing, regardless of temperature and time. The obtained poly(L-lactide) films exhibiting liquid crystal properties were subjected to degradation tests and the influence of degradation on these properties was determined. Thermotropic phase behavior was investigated using polarized optical microscopy, X-ray diffraction, and differential scanning calorimetry. The degradation process demonstrated an influence on the liquid crystal properties of pressed polymer films. The colored planar texture of the chiral nematic mesophase, which was not observed prior to degradation in films without the addition of β-cyclodextrin, appeared after incubation in water as a result of the entrapment of degradation products in the polymer matrix. These unusual tailor-made properties, obtained in liquid crystals in (bio)degradable polymers using a simple method, demonstrate the potential for advanced photonic applications.

Trans-Resveratrol Decreases Membrane Water Permeability: A Study of Cholesterol-Dependent Interactions.

Resveratrol (RSV), a biologically active plant phenol, has been extensively investigated for cancer prevention and treatment due to its ability to regulate intracellular targets and signaling pathways which affect cell growth and metastasis. The non-specific interactions between RSV and cell membranes can modulate physical properties of membranes, which in turn can affect the conformation of proteins and perturb membrane-hosted biological functions. This study examines non-specific interactions of RSV with model membranes having varying concentrations of cholesterol (Chol), mimicking normal and cancerous cells. The perturbation of the model membrane by RSV is sensed by changes in water permeability parameters, using Droplet Interface Bilayer (DIB) models, thermotropic properties from Differential Scanning Calorimetry, and structural properties from confocal Raman spectroscopy, all of which are techniques not complicated by the use of probes which may themselves perturb the membrane. The nature and extent of interactions greatly depend on the presence and absence of Chol as well as the concentration of RSV. Our results indicate that the presence of RSV decreases water permeability of lipid membranes composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), indicating a capability for RSV in stiffening fluidic membranes. When Chol is present, however, (at 4:1 and 2:1mol ratio DOPC to cholesterol), the addition of RSV has no significant effect upon the water permeability. DSC thermograms show that RSV interacts with DOPC and DOPC/Chol bilayers and influences their thermotropic phase behavior in a concentration-dependent manner, by decreasing the main phase transition temperature and enthalpy, with a phase separation shown at the higher concentrations of RSV. Raman spectroscopic studies indicate an ordering effect of RSV on DOPC supported bilayer, with a lesser extent of ordering in the presence of Chol. Combined results from these investigations highlight a differential effect of RSV on Chol-free and Chol-enriched membranes, respectively, which results constitute a bellwether for increased understanding and effective use of resveratrol in disease therapy including cancer.

Block copolymer self-assembly: Melt and solution by molecular density functional theory.

The self-assembly of block copolymer melts and solutions with two-dimensional density inhomogeneity is studied using modified inhomogeneous statistical associating fluid theory (iSAFT). A real-space combinatorial screening method under density functional theory formalism is proposed and used to map out the phase diagram of block copolymer melts including order-disorder transitions and order-order transitions. The predicted phase diagram agrees well with molecular dynamics simulation and self-consistent field theory. The compressibility effect on order-disorder transition temperature for block copolymer melts is modeled using iSAFT. The pressure induced temperature change by theory has a similar trend to experimental studies. Then, the lyotropic and thermotropic self-assembly phase behavior of block copolymer solutions is investigated. Detailed density distributions by iSAFT provide insight into the lyotropic properties of the block copolymer solutions at the molecular level. The effect of the block copolymer molecular architecture is studied by comparing block copolymers with different molecular packing parameters. Block copolymer solutions in the inverted hexagonal phase are predicted by theory for the block copolymer having a large molecular packing parameter. Finally, solvent selectivity is studied by modeling the block copolymers in a neutral good solvent. The enhanced local solvent concentration predicted by theory explains the reason for fewer ordered phases found in experiments.

Insights into molecular mechanism of action of citrus flavonoids hesperidin and naringin on lipid bilayers using spectroscopic, calorimetric, microscopic and theoretical studies

Hesperidin and naringin are predominant flavonoids in citrus fruits and exert various biological activities. However, mechanism of these activities has not been completely investigated at cellular and molecular levels. For this reason, we aim to systematically elucidate molecular interactions between citrus flavonoids, hesperidin and naringin, and model lipid membranes composed of dimyristoylphosphatidylcholine (DMPC) using combinatorial experimental biophysical techniques, attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, differential scanning calorimetry (DSC), atomic force microscopy (AFM) and field emission scanning electron microscopy (FE-SEM) as a function of citrus flavonoid concentrations, and computational study. ATR-FTIR showed that both flavonoids significantly increase the fluidity of DMPC membranes with the increase in the bandwidth values of the CH2 antisymmetric stretching vibration. While hesperidin exhibits weakly disordering effect in hydrophobic region, naringin has an ordering effect in this region. Both flavonoids induce alterations in the arrangement of polar heads of lipids. DSC revealed that naringin significantly influences the cooperativity and thermotropic phase behavior of DMPC compared to hesperidin. Furthermore, microscopic observations are in cooperation with the spectroscopic and calorimetric results indicating that naringin is more effective than hesperidin in terms of inducing changes in the membrane organization. Density functional theory (DFT) study demonstrated that both DMPC − Hesperidin and DMPC − Naringin systems form strong hydrogen bonding via PO2− moieties. Methodologies showed that small structural differences can influence the membrane bilayers distinctly. Consequently, this study implies that variations in structural and dynamical properties of lipid membranes can be critical for processes involving the inhibition of lipid peroxidation and antioxidant mechanism.

Single Enzyme Nanoparticles with Improved Biocatalytic Activity through Protein Entrapment in a Surfactant Shell.

A polymeric corona consisting of an alkyl-glycolic acid ethoxylate (CXEOY) surfactant offers a promising approach toward endowing proteins with thermotropic phase behavior and hyperthermal activity. Typically, preparation of protein–surfactant biohybrids is performed via chemical modification of acidic residues followed by electrostatic conjugation of an anionic surfactant to encapsulate single proteins. While this procedure has been applied to a broad range of proteins, modification of acidic residues may be detrimental to function for specific enzymes. Herein, we report on the one-pot preparation of biohybrids via covalent conjugation of surfactants to accessible lysine residues. We entrap the model enzyme hen egg-white lysozyme (HEWL) in a shell of carboxyl-functionalized C12EO10 or C12EO22 surfactants. With fewer surfactants, our covalent biohybrids display similar thermotropic phase behavior to their electrostatically conjugated analogues. Through a combination of small-angle X-ray scattering and circular dichroism spectroscopy, we find that both classes of biohybrids consist of a folded single-protein core decorated by surfactants. Whilst traditional biohybrids retain densely packed surfactant coronas, our biohybrids display a less dense and heterogeneously distributed surfactant coverage located opposite to the catalytic cleft of HEWL. In solution, this surfactant coating permits 7- or 3.5-fold improvements in activity retention for biohybrids containing C12EO10 or C12EO22, respectively. The reported alternative pathway for biohybrid preparation offers a new horizon to expand upon the library of proteins for which functional biohybrid materials can be prepared. We also expect that an improved understanding of the distribution of tethered surfactants in the corona will be crucial for future structure–function investigations.

Structure, thermotropic phase behavior and membrane interaction of N-acyl-β-alaninols. Homologs of stress-combating N-acylethanolamines

β-Alaninol and its derivatives were reported to exhibit interesting biological and pharmacological activities and showed potential application in formulating drug delivery vehicles. In the present study, we report the synthesis and characterization of N-acyl-β-alaninols (NABAOHs) bearing saturated acyl chains (n = 8–20) with respect to thermotropic phase behavior, supramolecular organization and interaction with diacylphosphatidylcholine, a major membrane lipid. Results obtained from DSC and powder XRD studies revealed that the transition temperatures (Tt), transition enthalpies (ΔHt), transition entropies (ΔSt) and d-spacings of NABAOHs show odd-even alteration. A linear dependence was observed in the values of ΔHt and ΔSt on the acyl chain length, independently for even and odd acyl chains in both dry and hydrated states; further, the even chainlength molecules exhibited higher values than the odd chainlength series. The crystals structures of N-lauroyl-β-alaninol and N-palmitoyl-β-alaninol, solved in monoclinic system in the P21/c space group, show that the NABAOHs adopt a tilted bilayer structure. A number of NH⋯O, O—H⋯O, and C—H⋯O hydrogen bonds between the hydroxyl and amide moieties of the head groups of NABAOH molecules belonging to adjacent and opposite layers stabilize the overall supramolecular organization of the self-assembled bilayer system. DSC studies on the interaction of N-myristoyl-β-alaninol (NMBAOH) with dimyristoylphosphatidylcholine (DMPC) indicate that these two lipids mix well up to 45 mol% NMBAOH, whereas phase separation was observed at higher contents of NMBAOH. Transmission electron microscopic studies reveal that mixtures containing 20−50 mol% NMBAOH form stable ULVs of 90−150 nm diameter, suitable for use in drug delivery applications.

Coarse-grained simulations of ionic liquid materials: from monomeric ionic liquids to ionic liquid crystals and polymeric ionic liquids.

Ionic liquid (IL) materials are promising electrolytes with striking physicochemical properties for energy and environmental applications. Heterogeneous structures and transport quantities of monomeric and polymeric ILs are intrinsically intercorrelated and span multiple spatiotemporal scales, which is more feasible for coarse-grained (CG) simulations than atomistic modelling. Herein we constructed a novel CG model for ethyl-imidazolium tetrafluoroborate ILs with varied cation alkyl chains ranging from C2 to C20, and the interaction parameters were validated against representative static and dynamic properties that were obtained from atomistic reference simulations and experimental characterizations at relevant thermodynamic states. This CG model was extended to study thermotropic phase behaviors of monomeric ILs and to explore ion association structures and ion transport quantities in polymeric ILs with different architectures. A systematic analysis of structural and dynamical quantities identifies an evolution of liquid morphology from homogeneous to nanosegregated structures and then a smectic mesomorphism via a gradual lengthening of cation alkyl chains, and thereafter a distinct structural transition characterized by a monotonic decrease in orientational and translational order parameters in a sequential heating cascade. Backbone and pendant polymeric ILs exhibit evident anion association structures with cation monomers and polymer chains, and striking intra- and interchain coordinations between cation monomers owing to an intrinsic polymer architecture effect. Such a peculiar ion pairing association leads to a progressive increase in anion intrachain hopping probabilities, and a concomitant decrease in anion interchain hopping events with a gradual lengthening of polymeric ILs. The anion diffusivities in polymeric ILs are intrinsically correlated with ion pairing association lifetimes and ion structural relaxation times via a universal power law correlation D ∼ τ-1, irrespective of polymer architectures.

Loading of lutein in egg-sphingomyelin vesicles as lipid carriers: Thermotropic phase behaviour, structure of sphingosome membranes and lutein crystals

Lutein is a xanthophyll carotenoid provided exclusively by the diet, that has protective functions and beneficial effects on human health. Supplementation in lutein is necessary to reach the recommended daily dietary intake. However, the introduction of lutein into foods and beverages is a real challenge since this lipophilic nutrient has a poor aqueous solubility and a low bioavailability. In this study, we investigated the capacity of egg-sphingomyelin (ESM) vesicles called sphingosomes to solubilise lutein into the bilayers. The thermal and structural properties of ESM bilayers were examined in presence of various amounts of lutein by differential scanning calorimetry (DSC) and temperature-controlled X-ray diffraction (XRD), the structures of sphingosomes and lutein crystals were observed by microscopic techniques. ESM bilayers were in the fluid Lα phase above the phase transition temperature Tm = 39.6 °C and in the lamellar ripple Pβ′ phase below Tm where ESM sphingosomes exhibited ondulations and were facetted. Lutein molecules were successfully incorporated into the ESM bilayers where they induced a structural disorganisation. For ESM/lutein 90/10 %mol (91.8/8.2 %wt; 89 mg lutein / g ESM), lutein partitioning occured with the formation of lutein crystals in the aqueous phase together with lutein-loaded ESM vesicles. This study highlighted the capacity of new lipid carriers such as egg-sphingosomes to solubilise lutein and opens perspectives for the formulation of effective lutein-fortified functionnal foods and beverages providing health benefits.

Binding of warfarin differently affects the thermal behavior and chain packing of anionic, zwitterionic and cationic lipid membranes

Warfarin is a coumarin derivative drug widely used for its anticoagulant properties. The interaction of warfarin with fully hydrated lipid bilayers has been studied by combining differential scanning calorimetry, spectrophotometry, electron spin resonance of chain-labelled lipids and molecular docking. Bilayers formed by lipids with different chemico-physical properties were considered, namely dimyristoyl-phosphatidylcholine (DMPC), dimyristoyl-phosphatidylglycerol (DMPG), and dioleoyltrimethyl-ammoniumpropane (DOTAP). We observed in all cases the binding of warfarin in proximity of the surface of the bilayers, leading to a variety of distinct effects on key molecular properties of the membranes. The drug associates with the lipid bilayers in the deprotonated open chain form, with an association constant similar for DMPC and DMPG (1.27·104 and 2.82·104 M−1, respectively) and lower for DOTAP (0.46·104 M−1). In DMPC bilayers, which are zwitterionic and with saturated symmetrical chains, warfarin at 10 mol% suppresses the pre-transition, slightly stabilizes the fluid state and reduces the cooperativity of the main transition. Moreover, it alters the lateral packing density of the chain segments close to the polar/apolar interface at any temperature through the gel phase. In anionic DMPG bilayers, the drug slightly perturbs the thermotropic phase behavior, and at 10 mol% markedly loosens the compact gel phase packing of the first chain segments. In cationic DOTAP bilayers, possessing unsaturated acyl chains, the drug induces a slightly higher degree of order and motional restriction in the outer hydrocarbon region in the frozen state. In all cases, as a surface adsorbed molecule, warfarin does not affect the segmental chain order and dynamics for temperatures in the fluid phase. The overall results provide an outline of the action of warfarin on membranes formed by lipids of different types.

Dioctadecyldimethylammonium bromide, a surfactant model for the cell membrane: Importance of microscopic dynamics.

Cationic lipid membranes have recently attracted huge attention both from a fundamental point of view and due to their practical applications in drug delivery and gene therapy. The dynamical behavior of the lipids in the membrane is a key parameter controlling various physiological processes and drug release kinetics. Here, we review the dynamical and thermotropic phase behavior of an archetypal cationic lipid membrane, dioctadecyldimethylammonium bromide (DODAB), as studied using neutron scattering and molecular dynamics simulation techniques. DODAB membranes exhibit interesting phase behavior, specifically showing coagel, gel, and fluid phases in addition to a large hysteresis when comparing heating and cooling cycles. The dynamics of the lipid membrane is strongly dependent on the physical state of the bilayer. Lateral diffusion of the lipids is faster, by an order of magnitude, in the fluid phase than in the ordered phase. It is not only the characteristic times but also the nature of the segmental motions that differ between the ordered and fluid phases. The effect of different membrane active molecules including drugs, stimulants, gemini surfactants, and unsaturated lipids, on the dynamical and thermotropic phase behavior of the DODAB membrane, is also discussed here. Various interesting features such as induced synchronous ordering between polar head groups and tails, sub diffusive behavior, etc., are observed. The results shed light on the interaction between these additives and the membrane, which is found to be a complex interplay between the physical state of the membrane, charge, concentration, molecular architecture of the additives, and their location within the membrane.

Stereochemical Purity Can Induce a New Crystalline Mesophase in Phytantriol Lipids.

The impact of stereochemical purity of lipids on their self-assembly behavior is critical for establishing their true phase behavior from their commercial counterparts, which often contains stereoisomeric mixtures and other impurities. Here, stereochemically pure phytantriol (PT), (3,7,11,15-tetramethylhexadecane-1,2,3-triol) was synthesized from the natural trans-phytol and its thermotropic and lyotropic phase behavior in water investigated by small-angle X-ray scattering (SAXS), polarized optical microscopy (POM), and differential scanning calorimetry (DSC). These chemically pure lipids contain two chiral centers at the hydrophilic head group region and two chiral centers at the lipophilic tail region, allowing us to address the question of whether the molecular stereochemistry is related to the macroscopic phase behavior of phytantriol. In contrast to its commercial stereoisomeric mixtures, which form an isotropic micellar phase, neat (2S,3S,7R,11R)-3,7,11,15-tetramethylhexadecane-1,2,3-triol (S,S-PT) shows a smectic lamellar phase at room temperature, whereas (2R,3R,7R,11R)-3,7,11,15-tetramethylhexadecane-1,2,3-triol (R,R-PT) forms solid crystals. The lyotropic phase behavior of R,R-PT appears to be identical to that of the previously reported commercial stereoisomeric PT mixtures. In contrast, S,S-PT exhibits a different phase behavior. A lamellar crystalline phase (Lc) is formed instead of an isotropic micellar phase at a low water content, which also coexisted with other phases at low temperature. Subtle change in the shape of the diastereomers leads to variable steric interactions and subsequently affects the packing of the lipids at the molecular level, thereby influencing its self-assembling behavior. Finally, lipidic cubic phase crystallization of the membrane protein bacteriorhodopsin yielded a larger number of microcrystals with a higher average crystal length from S,S-PT than from commercial PT, suggesting faster nucleation.