Gel-liquid Phase Research Articles

Retraction: Two-step naked-eye detection of lectin by hierarchical organization of soft nanotubes into liquid crystal and gel phases.

Retraction of 'Two-step naked-eye detection of lectin by hierarchical organization of soft nanotubes into liquid crystal and gel phases' by Naohiro Kameta et al., Chem. Commun., 2015, 51, 6816-6819, https://doi.org/10.1039/C5CC01464F.

Methyl-β-cyclodextrin asymmetrically extracts phospholipid from bilayers, granting tunable control over differential stress in lipid vesicles.

Lipid asymmetry - that is, a nonuniform lipid distribution between the leaflets of a bilayer - is a ubiquitous feature of biomembranes and is implicated in several cellular phenomena. Differential tension - that is, unequal lateral monolayer tensions comparing the leaflets of a bilayer- is closely associated with lipid asymmetry underlying these varied roles. Because differential tension is not directly measurable in combination with the fact that common methods to adjust this quantity grant only semi-quantitative control over it, a detailed understanding of lipid asymmetry and differential tension are impeded. To overcome these challenges, we leveraged reversible complexation of phospholipid by methyl-β-cyclodextrin (mbCD) to tune the direction and magnitude of lipid asymmetry in synthetic vesicles. Lipid asymmetry generated in our study induced (i) vesicle shape changes and (ii) gel-liquid phase coexistence in 1-component vesicles. By applying mass-action considerations to interpret our findings, we discuss how this approach provides access to phospholipid thermodynamic potentials in bilayers containing lipid asymmetry (which are coupled to the differential tension of a bilayer). Because lipid asymmetry yielded by our approach is (i) tunable and (ii) maintained over minute to hour timescales, we anticipate that this approach will be a valuable addition to the experimental toolbox for systematic investigation into the biophysical role(s) of lipid asymmetry (and differential tension).

Molecular mechanism of the anti-gastric cancer activity of 1,2,3,6-tetra-O-galloyl-β-D-glucose isolated from Trapa bispinosa Roxb. shell in vitro.

Trapa bispinosa Roxb. is a traditional Chinese food which is well known for its medicinal properties. The shell of Trapa bispinosa has anticancer activity, maybe due to its high content of polyphenols. There are few studies on the chemical composition of Trapa bispinosa shells, then we isolated the active components from Trapa bispinosa shell and clarified the mechanism of its anticancer activity. One monomer compound was separated from the ethanol extract of the Trapa bispinosa shell by fractional extraction, silica gel, Sephadex LH-20 gel column chromatography and liquid phase separation. The structure, identified by NMR was 1,2,3,6-tetra-O-galloyl-β-D-glucose. The results of the CCK-8 assay showed that 1,2,3,6-tetra-O-galloyl-β-D-glucose could significantly inhibit the proliferation of gastric cancer SGC7901 cells, and the effect was close to that of 5-fluorouracil. Here, 1,2,3,6-tetra-O-galloyl-β-D-glucose could affect the cell cycle of SGC7901 cells. At the dose of 200 μg/mL and an incubation time of 48 h, SGC7901 cells remained in the G1 phase, apoptosis occurred, the intracellular calcium ion concentration increased and the mitochondrial membrane potential decreased. Transcriptome sequencing analysis showed that the differentially expressed genes were mainly enriched in the P53 signalling pathway associated with apoptosis. The results of qPCR and Western blot showed that 1,2,3,6-tetra-O-galloyl-β-D-glucose could induce apoptosis of SGC7901 cells by up-regulating the expression levels of P21, PUMA, PERP and IGF-BP3 genes, down-regulating the CyclinD gene, increasing the expression levels of cytochrome C, caspase-3, caspase-9 protein and decreasing that of the protein BCL-2.

Phase transitions of liposomes: when light meets heat

Phase transitions of liposomes are normally studied by differential scanning calorimetry. A suspension of liposomes is subjected to an increase (decrease) of temperature and when heat is absorbed (released), the liposomes transit from a gel (liquid) to a liquid (gel) phase. This endothermic (exothermic) process takes place at a temperature called the melting temperature T m, which is distinctive of the type of lipids forming the vesicles. The vesicles, though, also modify their size in the transition. Indeed, the thickness of the membranes decreases (increases) because carbon tails misalign (align). Concomitant with the modifications in the membrane thickness, the diameter (D) of the liposomes changes too. Therefore, when they are inspected by light, the scattered signal carries information from such dilatation (contraction) process. We performed careful experiments using dynamic light scattering as a function of temperature to detect the size changes of different liposomes. Gaussian fits of the derivatives of the D vs T curves coincide within 1% with thermograms, which hints to the possibility of performing thermodynamic studies of lipid systems employing light.

Two-step hydrothermal synthesis and conversion mechanism of zeolite X from stellerite zeolite.

We investigated the conversion mechanism of stellerite zeolite to zeolite X under two-step hydrothermal conditions. To elucidate the conversion mechanism, solid products were separated from the mixtures at different crystallization times and characterized by XRD, FESEM, FT-IR, Raman, solid-state NMR, XRF, and TEM. The results indicate that in this reaction process, the Si, Al, and Na in the gel solid phases were continuously dissolved and transformed into the gel–liquid-phase. When the concentration of each component reached supersaturation in the gel–liquid-phase, Si, Al, and Na were transferred to the surface of the gel–solid-phase, and nucleation and crystallization occurred on the surface. Abundant nuclei were formed during the second hour of the crystallization. As the crystallization time increased, the nuclei rapidly grew into zeolite X crystals, and the relative crystallinity of zeolite X reached a maximum when the crystallization time reached 4 h. These phenomena indicate that the formation mechanism of zeolite X is a liquid-phase conversion mechanism.

Small-angle X-ray (SAXS) and Raman spectroscopy studies of biot-CMG(2)-DOPE quasicrystalline phases

Neoglycolipids due to their amphiphilic properties exhibit self-assembly in aqueous phases. In high concentrations the liquid crystalline or gel phases may form. So-called soft-material are a subject of interest of many scientists especially as biosensors and wound healing materials. In this study we examine the structure of a quasicrystalline phase of biot-CMG(2)-DOPE obtained at the concentration of 150 mg/ml (13wt.%) in PBS. The structural data such as interplanar spacing, order parameter and long-range order were obtained by SAXS, while the changes in chemical structure were studied by Raman spectroscopy. It was also in our interest to examine a correlation between the ionic strength and the self-assembly, so we also studied a similar quasicrystalline phase of the same compound but in a buffer containing CaCl2 at the concentration of 4wt.%. According to SAXS data, FSL-biotin construct formed a complex ordered phase consisting of overlapping latices of different kind. The addition of CaCl2 into PBS resulted in obtaining a more structured system demonstrating cubic-like crystal lattice. Change in peak intensities on Raman spectrums of -C-H- and -C-C- bonds vibrations explained the change in phase properties.

Self-dispersing self-assembling systems for controlled oral delivery of gliclazide

Self-microemulsifying systems undergo self-dispersion to form microemulsion with subsequent self-assembly to form liquid crystalline (LC) and/or gel phases. These transitions modulate the release and absorption pattern of loaded drug. Accordingly, the primary objective was to evaluate these phases with respect to gliclazide release and absorption after oral administration. Pseudoternary phase diagrams were constructed using Peceol as oil, Gelucire 50/13 as surfactant and Transcutol as co-surfactant with Gelucire and Transcutol being used at 1:1 or 2:1, weight ratios. Microemulsion, LC and gel formulations were selected from these phase diagrams and were loaded with gliclazide. The selected systems were evaluated for gliclazide release which was conducted using continuous pH variation to mimic the gastrointestinal conditions. Optimum systems were subjected to in vivo evaluation. The in vivo study involved monitoring blood glucose level of diabetic rats after oral administration of gliclazide in aqueous suspension, microemulsion, LC and gel systems. Microemulsion liberated gliclazide rapidly and the rate of drug release was reduced in case of LC with further slowing in case of gel system. Interestingly, LC and gel systems liberated gliclazide steadily via zero order release kinetics. Microemulsion provided rapid reduction of blood glucose level but was not able to sustain this effect. LC and gel systems provided sustained effect and enhanced the bioavailability as shown from significant increase in the area under glucose reduction curve compared to both microemulsion and suspension form. The study thus introduced LC and gel phase as controlled release systems for oral delivery of gliclazide.

Micro-structural investigations on oppositely charged mixed surfactant gels with potential dermal applications

Dicarboxylic amino acid-based surfactants (N-dodecyl derivatives of -aminomalonate, -aspartate, and -glutamate) in combination with hexadecyltrimethylammonium bromide (HTAB) form a variety of aggregates. Composition and concentration-dependent mixtures exhibit liquid crystal, gel, precipitate, and clear isotropic phases. Liquid crystalline patterns, formed by surfactant mixtures, were identified by polarizing optical microscopy. FE-SEM studies reveal the existence of surface morphologies of different mixed aggregates. Phase transition and associated weight loss were found to depend on the composition where thermotropic behaviours were revealed through combined differential scanning calorimetry and thermogravimetric studies. Systems comprising more than 60 mol% HTAB demonstrate shear-thinning behaviour. Gels cause insignificant toxicity to human peripheral lymphocytes and irritation to bare mouse skin; they do not display the symptoms of cutaneous irritation, neutrophilic invasion, and inflammation (erythema, edema, and skin thinning) as evidenced by cumulative irritancy index score. Gels also exhibit substantial antibacterial effects on Staphylococcus aureus, a potent causative agent of skin and soft tissue infections, suggesting its possible application as a vehicle for topical dermatological drug delivery.

A novel electronic assay based on a sol-gel transition reaction and a thin-film transistor of supramolecular hydrogels to detect alkaline phosphatase activity

Abstract Herein, we developed an extended floating-gate thin-film transistor (EFG-TFT) together with various sol-gel phases to determine alkaline phosphatase (ALP) activity. The EFG-TFT was fabricated with ZnO as the channel material and YOX as the dielectric layer, which provided an extended area for sensing the analyte interacting with the designed hydrogelator. A peptide-based supramolecular hydrogel material, i.e., 2-naphthylacetic acid- l -phenylalanine- l -phenylalanine- l -O-phosphor tyrosine (named Nap-FF-Yp) was synthesized as our sensing platform to detect ALP activity and the sol-gel state. Nap-FF-Yp could be cleaved by ALP during hydrolysis, leading to π-π stacking, and finally changed to a hydrogel. Due to the difference in the potential drop between the liquid phase and gel phase of the hydrogel, the sol-gel transition reaction could be monitored by the electrical signal. The greater the extent of hydrogelation, the smaller the threshold voltage (Vth) variation, and the threshold voltage shifted to the left. Under the device’s optimal conditions with oxygen plasma treatment, the limit of detection (LOD) reached 0.024 U/L. The development of this novel sol-gel state for a high-speed screening sensing platform with an excellent electrical response demonstrates the potential capabilities of future high-speed response sensors.

Origin of lipid tilt in flat monolayers and bilayers.

This paper continues the series of our works devoted to the liquid-gel phase transition in lipid membranes. Previously we described a variation of area per lipid, membrane thickness, and diffusion coefficient at the temperature-driven liquid-gel phase transition in bilayers. Here we expand the application of our analytic model approach to include a description of the lipid tilt and also extend the investigation to include Langmuir and self-assembled monolayers. The theory describes tilt formation at the temperature-driven liquid-gel phase transition in bilayers and the pressure-driven phase transition in Langmuir monolayers. Neither uniform tilt nor liquid-gel phase transition is found in self-assembled monolayers chemically bonded to the substrate.

Life in Phases: Intra- and Inter- Molecular Phase Transitions in Protein Solutions.

Proteins, these evolutionarily-edited biological polymers, are able to undergo intramolecular and intermolecular phase transitions. Spontaneous intramolecular phase transitions define the folding of globular proteins, whereas binding-induced, intra- and inter- molecular phase transitions play a crucial role in the functionality of many intrinsically-disordered proteins. On the other hand, intermolecular phase transitions are the behind-the-scenes players in a diverse set of macrosystemic phenomena taking place in protein solutions, such as new phase nucleation in bulk, on the interface, and on the impurities, protein crystallization, protein aggregation, the formation of amyloid fibrils, and intermolecular liquid–liquid or liquid–gel phase transitions associated with the biogenesis of membraneless organelles in the cells. This review is dedicated to the systematic analysis of the phase behavior of protein molecules and their ensembles, and provides a description of the major physical principles governing intramolecular and intermolecular phase transitions in protein solutions.

Ionic Liquid Gels: Supramolecular Reaction Media for the Alcoholysis of Anhydrides.

The search of new enantioselective catalysts, able to promote synthetically useful organic reactions with high levels of asymmetric induction, should be associated with the attention to the suitable reaction medium able to achieve the best efficiency in chemical processes. We have investigated the enantioselective desymmetrization of cyclic meso-anhydrides in nonconventional reaction media such as ionic liquids and supramolecular gels. With this aim, we examined several variables in the reacting system: the nature of ionic liquid used as the reaction medium, the gelation solvent, the structure of the anhydrides, the structure of alcohols, the chiral catalysts, and the reaction conditions, i.e., temperature and time. The different components of the system differently influence the reaction outcome, and to understand the interactions existing among them, 1H NMR investigation was carried out. In general, the nonconventional reaction media demonstrated better performance than conventional ones, applying only a small amount of solvent. Good results in terms of yield and enantiomeric excess have been obtained in ionic liquid gels that seem promising media in the catalytic field. Furthermore, to the best of our knowledge, this is one of the first examples for the study of asymmetric alcoholysis of anhydrides in ionic liquid solution and gel phase.

Lipid lateral self-diffusion drop at liquid-gel phase transition.

A drop of lipid lateral self-diffusion coefficient at the liquid-gel phase transition in lipid membranes is calculated. So far this drop was missing theoretical description. Our microscopic model captures so-called subdiffusion regime, which takes place on 1 ps-100 ns timescale and reveals a jump of self-diffusion coefficient. Calculation of the jump is based on our recent study of liquid-gel phase transition. Subdiffusive regime is described within the free volume theory. Calculated values of self-diffusion coefficient are in agreement with quasielastic neutron scattering measurements. Self-diffusion coefficient is found to be composed of two factors: one is related to an area per lipid change at the phase transition, and the other one is due to an order of magnitude change in the stiffness of entropic repulsive potential.

Microscopic Description of the Thermodynamics of a Lipid Membrane at a Liquid–Gel Phase Transition

A microscopic model of the lipid membrane is constructed that provides analytically tractable description of the physical mechanism of the first order liquid-gel phase transition. We demonstrate that liquid-gel phase transition is cooperative effect of the three major interactions: inter-lipid van der Waals attraction, steric repulsion and hydrophobic tension. The model explicitly shows that temperature-dependent inter-lipid steric repulsion switches the system from liquid to gel phase when the temperature decreases. The switching manifests itself in the increase of lateral compressibility of the lipids as the temperature decreases, making phase with smaller area more preferable below the transition temperature. The model gives qualitatively correct picture of abrupt change at transition temperature of the area per lipid, membrane thickness and volume per hydrocarbon group in the lipid chains. The calculated dependence of phase transition temperature on lipid chain length is in quantitative agreement with experimental data. Steric repulsion between the lipid molecules is shown to be the only driver of the phase transition, as van der Waals attraction and hydrophobic tension are weakly temperature dependent.

Analytical Calculation of Diffusion Coefficient Drop at the Liquid-Gel Phase Transition in Lipid Membrane

Diffusion coefficient drop by an order of magnitude at the liquid-gel phase transition in the lipid membranes so far was missing theoretical description. Subdiffusion regime, which takes place on 1ps-10ns timescale, is captured by our microscopic model and shows a jump of the self-diffusion coefficient. We developed the analytical theory of the first order liquid-gel phase transition of a lipid bilayer using the microscopic model of semi-flexible strings. We have shown that the van der Waals attraction between the lipids tails is the essential component of the free energy. In the framework of the free volume theory, we calculated a diffusion coefficient in the subdiffusive regime drop by an order of magnitude at the main phase transition. We found that the main contribution to the diffusion drop is due to compression factor as opposed to activation-like factor. The calculated temperature dependencies of the major thermodynamic characteristics of the lipid membranes including diffusion coefficient, membrane thickness, area and volume per lipid molecule are in a good quantitative agreement with experimental data. The work was supported by the Russian Science Foundation (project #17-79-20440).

Gel phase in hydrated calcium dipicolinate

The mineralization of dipicolinic acid (DPA) molecules in bacterial spore cores with Ca2+ ions to form Ca-DPA is critical to the wet-heat resistance of spores. This resistance to “wet-heat” also depends on the physical properties of water and DPA in the hydrated Ca-DPA-rich protoplasm. Using reactive molecular dynamics simulations, we have determined the phase diagram of hydrated Ca-DPA as a function of temperature and water concentration, which shows the existence of a gel phase along with distinct solid-gel and gel-liquid phase transitions. Simulations reveal monotonically decreasing solid-gel-liquid transition temperatures with increasing hydration, which explains the experimental trend of wet-heat resistance of bacterial spores. Our observation of different phases of water also reconciles previous conflicting experimental findings on the state of water in bacterial spores. Further comparison with an unmineralized hydrated DPA system allows us to quantify the importance of Ca mineralization in decreasing diffusivity and increasing the heat resistance of the spore.

Intramolecular structural parameters are key modulators of the gel-liquid transition in coarse grained simulations of DPPC and DOPC lipid bilayers

The capability of coarse-grained models based on the MARTINI mapping to reproduce the gel-liquid phase transition in saturated and unsaturated model lipids was investigated. We found that the model is able to reproduce a lower critical temperature for 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) with respect to 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Nonetheless, the appearance of a gel phase for DOPC is strictly dependent on the intramolecular parameters chosen to model its molecular structure. In particular, we show that the bending angle at the coarse-grained bead corresponding to the unsaturated carbon-carbon bond acts as an order parameter determining the temperature of the phase transition. Structural analysis of the molecular dynamics simulations runs evidences that in the gel phase, the packing of the lipophilic tails of DOPC assume a different conformation than in the liquid phase. In the latter phase, the DOPC geometry resembles that of the relaxed free molecule. DPPC:DOPC mixtures show a single phase transition temperature, indicating that the observation of a phase separation between the two lipids requires the simulation of systems with sizes much larger than the ones used here.

Erlang flow of hydrophilic pore formation and closure events in a lipid bilayer during phase transition resulting from diffusion in the radius space.

The Smoluchowski equation with an energy profile of a special type and an assumed hydrophobic ("half") pore source term is used to describe the process of hydrophilic pore formation in a lipid bilayer at the gel-liquid phase transition. The source term reflects the occurrence of molecule packing defects in a lipid bilayer at phase transition. The time sequences of the pore formation and closure events are treated as non-stationary, second-order Erlang flows whose characteristics depend on the equation solution. The computed distributions of the time intervals between hydrophilic pores, and pore lifetimes agree with the previously published experimental interpulse interval and pulse duration histograms for the current fluctuations through planar bilayer membranes of DPPC immersed in a LiCl aqueous solution containing polyethylene glycol. Thus, the statistical analysis of pore formation and closure times leads us to conclude that firstly, the increased permeability of a lipid bilayer during the gel-liquid phase transition is accounted for by the emergence of additional hydrophobic defects in the heterogeneous structure of the bilayer and secondly, that the non-exponential distributions of the lipid channel closed and open times observed in experiments are evidence that the process of hydrophilic pore formation is not a one-step process but involves at least two dependent events.

A green solvent holder in electro-mediated microextraction for the extraction of phenols in water

Electro-mediated microextraction (EMM) combined with micro-high performance liquid chromatography-ultraviolet detection was successfully developed for the determination of selected phenols, namely 4-chlorophenol (4CP), 2-nitrophenol (2NP) and 2,4-dichlorophenols (2,4 DCP) in water. A solvent-impregnated agarose gel disc was utilized as a solvent holder in this study. Under optimum extraction conditions, the method showed good linearity in the range of 0.1–250µgL−1, 0.3–250µgL−1 and 0.2–500µgL−1 for 4CP, 2NP and 2,4 DCP, respectively with correlation coefficients of ≥ 0.9975, ultra-trace LODs (0.03–0.1µgL−1) and satisfactory relative recovery average (85.0–114.1%) for the analysis of selected phenols. The proposed method was rapid and eco-friendly as the solvent holder was constructed using minute amounts of extraction solvent immobilized within the biodegradable agarose gel disc. A comparative microextraction technique termed solvent-impregnated agarose gel liquid phase microextraction (AG-LPME) was re-optimized and validated for the extraction of phenols in water. The method offered good linearity, ultra-trace LODs ranging 0.1–0.5µgL−1 and satisfactory average of relative recovery (86.1–114.1%). The EMM was superior in terms of sensitivity and time-effectiveness compared to AG-LPME. Both techniques combine extraction and pre-concentration in mini-scaled approaches using an eco-friendly solvent holder that fulfil the green chemistry concept.

Toward Chemically Resolved Computer Simulations of Dynamics and Remodeling of Biological Membranes

Cellular membranes are fundamental constituents of living organisms. Apart from defining the boundaries of the cells, they are involved in a wide range of biological functions, associated with both their structural and the dynamical properties. Biomembranes can undergo large-scale transformations when subject to specific environmental changes, including gel-liquid phase transitions, change of aggregation structure, formation of microtubules, or rupture into vesicles. All of these processes are dependent on a delicate interplay between intermolecular forces, molecular crowding, and entropy, and their understanding requires approaches that are able to capture and rationalize the details of all of the involved interactions. Molecular dynamics-based computational models at atom-level resolution are, in principle, the best way to perform such investigations. Unfortunately, the relevant spatial and time dimensionalities involved in membrane remodeling phenomena would require computational costs that are today unaffordable on a routinely basis. Such hurdles can be removed by coarse-graining the representations of the individual molecular components of the systems. This procedure anyway reduces the possibility of describing the chemical variations in the lipid mixtures composing biological membranes. New hybrid particle field multiscale approaches offer today a promising alternative to the more traditional particle-based simulations methods. By combining chemically distinguishable molecular representations with mesoscale-based computationally affordable potentials, they appear as one of the most promising ways to keep an accurate description of the chemical complexity of biological membranes and, at the same time, cover the required scales to describe remodeling events.