Glycolipid, found commonly in membranes, is also a liquid crystal material which can self-assemble without the presence of a solvent. Here, the dielectric and conductivity properties of three synthetic glycolipid thin films in different thermotropic liquid crystal phases were investigated over a frequency and temperature range of (10(-2)-10(6) Hz) and (303-463 K), respectively. The observed relaxation processes distinguish between the different phases (smectic A, columnar/hexagonal, and bicontinuous cubic Q) and the glycolipid molecular structures. Large dielectric responses were observed in the columnar and bicontinuous cubic phases of the longer branched alkyl chain glycolipids. Glycolipids with the shortest branched alkyl chain experience the most restricted self-assembly dynamic process over the broad temperature range studied compared to the longer ones. A high frequency dielectric absorption (Process I) was observed in all samples. This is related to the dynamics of the hydrogen bond network from the sugar group. An additional low-frequency mechanism (Process II) with a large dielectric strength was observed due to the internal dynamics of the self-assembly organization. Phase sensitive domain heterogeneity in the bicontinuous cubic phase was related to the diffusion of charge carriers. The microscopic features of charge hopping were modelled using the random walk scheme, and two charge carrier hopping lengths were estimated for two glycolipid systems. For Process I, the hopping length is comparable to the hydrogen bond and is related to the dynamics of the hydrogen bond network. Additionally, that for Process II is comparable to the bilayer spacing, hence confirming that this low-frequency mechanism is associated with the internal dynamics within the phase.
This study aimed at examining the biophysical characteristics of human derived keratinocytes (HaCaT) cultured on cholesteryl ester liquid crystals (CELC). CELC was previously shown to improve sensitivity in sensing cell contractions. Characteristics of the cell integrin expressions and presence of extracellular matrix (ECM) proteins on the liquid crystals were interrogated using various immunocytochemical techniques. The investigation was followed by characterization of the chemical properties of the liquid crystals (LC) after immersion in cell culture media using Fourier transform infrared spectroscopy (FTIR). The surface morphology of cells adhered to the LC was studied using atomic force microscopy (AFM). Consistent with the expressions of the integrins α2, α3 and β1, extracellular matrix proteins (laminin, collagen type IV and fibronectin) were found secreted by the HaCaT onto CELC and these proteins were also secreted by cells cultured on the glass substrates. FTIR analysis of the LC revealed the existence of spectrum assigned to cholesterol and ester moieties that are essential compounds for the metabolizing activities of keratinocytes. The immunostainings indicated that cell adhesion on the LC is mediated by self-secreted ECM proteins. As revealed by the AFM imaging, the constraint in cell membrane spread on the LC leads to the increase in cell surface roughness and thickness of cell membrane. The biophysical expressions of cells on biocompatible CELC suggested that CELC could be a new class of biological relevant material.
Cell migration is a key contributor to wound repair. This study presents findings indicating that the liquid crystal based cell traction force transducer (LCTFT) system can be used in conjunction with a bespoke cell traction force mapping (CTFM) software to monitor cell/surface traction forces from quiescent state in real time. In this study, time-lapse photo microscopy allowed cell induced deformations in liquid crystal coated substrates to be monitored and analyzed. The results indicated that the system could be used to monitor the generation of cell/surface forces in an initially quiescent cell, as it migrated over the culture substrate, via multiple points of contact between the cell and the surface. Future application of this system is the real-time assaying of the pharmacological effects of cytokines on the mechanics of cell migration.
Widefield surface plasmon resonance (WSPR) microscopy provides high resolution imaging of interfacial interactions. We report the application of the WSPR imaging system in the study of the interaction between keratinocytes and liquid crystals (LC). Imaging of fixed keratinocytes cultured on gold coated surface plasmon substrates functionalized with a thin film of liquid crystals was performed in air using a 1.45NA objective based system. Focal adhesion of the cells adhered to glass and LC were further studied using immunofluorescence staining of the vinculin. The imaging system was also simulated with 2×2 scattering matrix to investigate the optical reflection of the resonant plasmonic wave via the glass/gold/cell and glass/gold/LC/cell layers. WSPR imaging indicated that keratinocytes are less spread and formed distinct topography of cell-liquid crystal couplings when cultured on liquid crystal coated substrates. The simulation indicates that glass/LC shifted the surface plasmon excitation angle to 75.39° as compared to glass/air interface at 44°. The WSPR microcopy reveals that the cells remodelled their topography of adhesion at different interfaces.
Keratinocyte traction forces play a crucial role in wound healing. The aim of this study was to develop a novel cell traction force (CTF) transducer system based on cholesteryl ester liquid crystals (LC). Keratinocytes cultured on LC induced linear and isolated deformation lines in the LC surface. As suggested by the fluorescence staining, the deformation lines appeared to correlate with the forces generated by the contraction of circumferential actin filaments which were transmitted to the LC surface via the focal adhesions. Due to the linear viscoelastic behavior of the LC, Hooke's equation was used to quantify the CTFs by associating Young's modulus of LC to the cell induced stresses and biaxial strain in forming the LC deformation. Young's modulus of the LC was profiled by using spherical indentation and determined at approximately 87.1±17.2kPa. A new technique involving cytochalasin-B treatment was used to disrupt the intracellular force generating actin fibers, and consequently the biaxial strain in the LC induced by the cells was determined. Due to the improved sensitivity and spatial resolution (∼1μm) of the LC based CTF transducer, a wide range of CTFs was determined (10-120nN). These were found to be linearly proportional to the length of the deformations. The linear relationship of CTF-deformations was then applied in a bespoke CTF mapping software to estimate CTFs and to map CTF fields. The generated CTF map highlighted distinct distributions and different magnitude of CTFs were revealed for polarized and non-polarized keratinocytes.
Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.
Aim: In the present study, the inhibitory potential of rutin-loaded liquid crystalline nanoparticles (LCNs) on oxidative stress was determined in human bronchial epithelial cells (BEAS-2B) by analysing the expression levels of different antioxidant (NADPH quinine oxidoreductase-1 (NQO1); γ-glutamyl cysteine synthetase catalytic subunit (GCLC)) and pro-oxidant (NADPH oxidase (Nox)-4; Nox2B) genes. Results: Our findings revealed that the rutin-loaded LCNs inhibited the genes, namely Nox2B and Nox4, which caused oxidative stress. In addition, these nanoparticles demonstrated an upregulation in the expression of the antioxidant genes Gclc and Nqo-1 in a dose-dependent manner. Conclusion: The study indicates the promising potential of rutin-loaded LCNs as an effective treatment strategy in patients with high oxidant loads in various respiratory diseases.
Two series of new hexasubstituted cyclotriphosphazene derivatives were successfully synthesized and characterized. These derivatives are differentiated by two types of linking units in the molecules such as amide-azo (6a-j) and azo-azo (8a-j). The homologues of the same series contain different terminal substituents such as heptyl, nonyl, decyl, dodecyl, tetradecyl, hydroxyl, carboxyl, chloro, nitro, and amino groups. All the intermediates and final compounds were characterized using Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and Carbon, Hydrogen, and Nitrogen (CHN) elemental analysis. Liquid crystal properties for all compounds were determined using polarized optical microscope (POM). It was found that only intermediates 2a-e with nitro and alkoxyl terminal chains showed a smectic A phase. All the final compounds with alkoxyl substituents are mesogenic with either smectic A or C phases. However, other intermediates and compounds were found to be non-mesogenic. The study on the fire retardancy of final compounds was determined using limiting oxygen index (LOI) method. The LOI value of pure polyester resin (22.53%) was increased up to 24.71% after treating with 1 wt% of hexachlorocyclotriphosphazene (HCCP). Moreover, all the compounds gave positive results on the LOI values and compound 6i with the nitro terminal substituent showed the highest LOI value of 27.54%.
A series of new hexasubstituted cyclotriphosphazene compounds (4a-j) consisting of two Schiff base linking units and different terminal substituents was successfully synthesized and characterized. The structures of these compounds were confirmed using Fourier Transform Infra-Red (FTIR), Nuclear Magnetic Resonance (NMR), and CHN elemental analysis. Polarized optical microscopy (POM) was used to determine their liquid-crystal behavior, which was then further confirmed using differential scanning calorimetry (DSC). Compounds 4a-i with heptyl, nonyl, decyl, dodecyl, tetradecyl, hydroxy, 4-carboxyphenyl, chloro, and nitro terminal ends, respectively, showed the liquid-crystal properties, whereas compound 4j with the amino group was found to be non-mesogenic. The attachment of an electron-donating group in 4j eventually give a non-mesogenic product. The study of the fire-retardant properties of these compounds was done using the limiting oxygen index (LOI). In this study, polyester resin (PE) was used as a matrix for moulding, and the LOI value of pure PE was 22.53%. The LOI value increased to 24.71% when PE was incorporated with 1 wt.% of hexachlorocyclotriphosphazene (HCCP), thus indicating that HCCP has a good fire-retardant properties. The result showed that all the compounds have good agreement in their LOI values. Compound 4i with a nitro terminal group gave the highest LOI value of 28.37%.
Two new ether substituted azodyes were synthesized and characterized by different spectral analysis such as (1)H NMR, (13)C NMR, FTIR and UV/Vis. Synthesized compounds were used to study the photoisomerization phenomenon by using UV-Vis spectro-photometer. Interesting polarity dependent effect is observed for the first time on these materials. Trans-cis (E-Z) and cis-trans (Z-E) conversion occurred within 41 s and 445 min, respectively for both the compounds in solutions. Polarizing optical microscopy studies revealed that there is no liquid crystal phase for both the compounds. The dramatic variation in the optical property is speculated to be the polarity of the chemical species. These derivatives are useful to fabricate optical data storage devices.
The phenolic Schiff bases I-VI were synthesized by condensation reactions between various diamines, namely o-dianisidine, o-tolidine and ethylenediamine with vanillin or p-hydroxybenzaldehyde and subsequent reactions between these phenolic Schiff bases and epichlorohydrin to produce new diglycidyl ethers Ia-VIa. The structures of these compounds were confirmed by CHN, FT-IR, (1)H-NMR, and (13)C-NMR spectroscopy. Their thermotropic liquid crystalline behavior was studied using differential scanning calorimetry (DSC) and polarizing optical microscopy (POM). All the diglycidyl ethers prepared exhibit nematic mesophases, except for Va and VIa, which did not show any transition mesophases, but simply flow to liquids.
Through atomistic molecular dynamic simulations using a GROMOS53a6 force field for the carbohydrate, we studied the lyotropic reverse hexagonal phase HII from a glycolipid, namely the Guerbet branched-chain β-d-glucoside, at 14% and 22% water concentrations. Our simulations showed that at low water concentration (14%) the sugar head group overlapped extensively and protruded into the water channel. In contrast, in the 22% concentration system a water column free from the sugar headgroup ('free' water) was formed as expected for the system close to the limit of maximum hydration. In both concentrations, we found anomalous water diffusion in the xy-plane, i.e. the two-dimensional space confined by the surface of the cylinder. On the other hand, along the z-axis, the water diffusion obeyed the Einstein relation for the 22% system, while for the 14% system it was slightly anomalous. For the 22% system, the diffusion along the z-axis of the 'free' water obeyed the Einstein relation, while that of the 'bound' water is slightly anomalous. The xy-plane displacement of the 'bound' water was higher than that for the 'free' water at times longer than 200 ps, as a consequence of the exchange of water molecules between the two regions. Based on our findings, we proposed an alternative explanation to the observed spatial heterogeneity in the HII phase from probe diffusion by Penaloza et al. (Phys. Chem. Chem. Phys., 2012, 14(15), 5247-5250). We found the extent of contact with water was different at different oxygen atoms within the sugar ring. Generally, a higher probability of hydrogen bonding but a shorter lifetime was found in 22% water compared to the case of 14% water. Finally, we examined the extension and compression of the alkyl chain of a columnar.
Synthetic branched-chain glycolipids are suitable as model systems in understanding biological cell membranes, particularly because certain natural lipids possess chain branching. Herein, four branched-chain glycopyranosides, namely, 2-hexyl-decyl-α-D-glucopyranoside (α-Glc-OC10C6), 2-hexyl-decyl-β-D-glucopyranoside (β-Glc-OC10C6), 2-hexyl-decyl-α-D-galactopyranoside (α-Gal-OC10C6), and 2-hexyl-decyl-β-D-galactopyranoside (β-Gal-OC10C6), with a total alkyl chain length of 16 carbon atoms have been synthesized, and their phase behavior has been studied. The partial binary phase diagrams of these nonionic surfactants in water were investigated by optical polarizing microscopy (OPM) and small-angle X-ray scattering (SAXS). The introduction of chain branching in the hydrocarbon chain region is shown to result in the formation of inverse structures such as inverse hexagonal and inverse bicontinuous cubic phases. A comparison of the four compounds showed that they exhibited different polymorphism, especially in the thermotropic state, as a result of contributions from anomeric and epimeric effects according to their stereochemistry. The neat α-Glc-OC10C6 compound exhibited a lamellar (Lα) phase whereas dry α-Gal-OC10C6 formed an inverse bicontinuous cubic Ia3d (QII(G)) phase. Both β-anomers of glucoside and galactoside adopted the inverse hexagonal phase (HII) in the dry state. Generally, in the presence of water, all four glycolipids formed inverse bicontinuous cubic Ia3d (QII(G)) and Pn3m (QII(D)) phases over wide temperature and concentration ranges. The formation of inverse nonlamellar phases by these Guerbet branched-chain glycosides confirms their potential as materials for novel biotechnological applications such as drug delivery and crystallization of membrane proteins.
We have investigated the phase behavior of four glycosides (βC8OGlc, βC8SGlc, βC10OGlc, βC8OGal) in water and D2O by optical polarizing microscopy and deuterium NMR. Previously published phase diagrams were evaluated by deuterium NMR, via monitoring D2O spectra, and confirmed the presence of the hexagonal, bicontinuous cubic, and lamellar phases in these glycosides. We have also shown the presence of the gel phase in (βC10OGlc) and observed the extensive supercooling of the lamellar phase to temperatures well below the Kraft line. While the main features of the phase diagrams were confirmed, some phase boundaries were found to be slightly different. Magnetically aligned spectra were also observed for relatively dilute samples for the hexagonal phase (βC8OGlc and βC8OGal) and the lamellar phase (βC8SGlc and βC10OGlc). The average number of bound water molecules per headgroup in the lamellar phase for the glycosides was determined by the systematic measurement of the quadrupolar splitting of D2O over a wide range of values of the (glycoside/water) molar ratio. The number of water molecules bound to the headgroup was found on average to be about 1.6-1.7 water molecules with no significant differences in this value for the different glycosides (and over the temperature range investigated), indicating that the bound water content is predominately influenced by the number of hydroxyl groups of the headgroup only. However, this bound water content of only 1.6-1.7 water molecules per sugar headgroup is surprisingly low, suggesting strong intermolecular interactions of the OH groups of headgroup sugars. The results are in line with computational results reported earlier for the octyl-β-glucoside and β-galactoside, which show the presence of strong intralayer hydrogen bonding.
The molecular dynamics of a synthetic branched chain glycolipid, 2-decyl-tetradecyl-β-d-maltoside (C14-10G2), in the dry assemblage of smectic and columnar liquid crystal phases has been studied by dielectric spectroscopy as a function of frequency and temperature during the cooling process. Strong relaxation modes were observed corresponding to the tilted smectic and columnar phases, respectively. At low frequency (∼900 Hz to 1 kHz) in the smectic phase, Process I* was observed due to the tilted sugar bilayer structure. The process continued in the columnar phase (Process I) with an abrupt dynamic change due to phase transition in the frequency range of ∼1.3 kHz to 22 kHz. An additional process (Process II) was observed in the columnar phase with a broader relaxation in the frequency range of ∼10 Hz to 1 kHz. A bias field dependence study was performed in the columnar phase and we found that the relaxation strength rapidly decreased with increased applied dc bias field. This relaxation originates from a collective motion of polar groups within the columns. The results of dielectric spectroscopy were supported by a molecular dynamics simulation study to identify the origin of the relaxation processes, which could be related to the chirality and hydrogen bonds of the sugar lipid.
The lyotropic phase behavior of four common and easily accessible glycosides, n-octyl α-d-glycosides, namely, α-Glc-OC8, α-Man-OC8, α-Gal-OC8, and α-Xyl-OC8, was investigated. The presence of normal hexagonal (HI), bicontinuous cubic (VI), and lamellar (Lα) phases in α-Glc-OC8 and α-Man-OC8 including their phase diagrams in water reported previously was verified by deuterium nuclear magnetic resonance (2H NMR), via monitoring the D2O spectra. Additionally, the partial binary phase diagrams and the liquid crystal structures formed by α-Gal-OC8 and α-Xyl-OC8 in D2O were constructed and confirmed using small- and wide-angle X-ray scattering and 2H NMR. The average number of bound water molecules (nb) per headgroup in the Lα phase was determined by the systematic measurement of the quadrupolar splitting of D2O over a wide range of molar ratio values (glycoside/D2O), especially at high glucoside composition. The number of bound water molecules bound to the headgroup was found to be around 1.5-2.0 for glucoside, mannoside, and galactoside, all of which possesses four OH groups. In the case of xyloside, which has only three OH groups, the bound water content is ∼2.0. Our findings confirmed that the bound water content of all n-octyl α-d-glycosides studied is lower compared to the number of possible hydrogen bonding sites possibly due to the fact that most of the OH groups are involved in intralayer interaction that holds the lipid assembly together.
The first example of non-symmetric isoflavone-based fast photo-switchable liquid crystals with different functional groups at the terminal position were synthesized and characterized. Polarizing optical microscopy study revealed that the compounds showed least ordered nematic phase. Optical photo switching study exhibited very fast photoisomerization effect in solution. The E-Z and Z-E conversion occurred around 3-5s and 40-700 s respectively. This is also the first example of para-substituted non-symmetric isoflavone liquid crystals exhibiting very fast photo switching property in solution. Argument based on non-symmetrical behaviour might be the reason for the observed behaviour.
With the advancement of the fourth industrial revolution, the demand for LCD has widely accelerated as monitoring screens for computers and cell phones. Consequently, old LCD panels are expected to end up as a tremendous amount of e-waste. Apart from transparent electrodes and transistor, waste LCD panel also contains hazardous liquid crystal compound that can contaminate the landfill site. Thus, removing the material from waste LCD was investigated. In this study, water at subcritical state was applied at temperatures between 100 and 360 °C. Initially, the liquid crystals were extracted using toluene and were used to compare with subcritical water. The specific compounds of the liquid crystals were not identified. The liquid crystals (12 mg/g-LCD) were entirely removed from the LCD panel when treated above 300 °C by means of extraction with the subcritical water. Although liquid crystal was successfully removed, recovery was complicated due to the degradation of liquid crystals above 250 °C. A recovery of 70% was obtained at 250 °C without deformation of the molecules. Consequently, this study has shown that although it is not practical to recover LC from LCD panel waste using subcritical water, liquid crystals can be removed efficiently. This method is auspicious in reducing hazardous liquid crystal from waste LCD panel before their disposals at landfill sites.
Lyotropic nonlamellar liquid crystalline nanoparticles (NPs) (LCN), such as cubosomes and hexosomes, are useful tools for applications in drug delivery because of their unique structural properties. LCNs are highly versatile carriers that can be applied for use with topical, oral, and intravenous treatments. In recent years, significant research has focused on improving their preparation and characterization, including controlling drug release and enhancing the efficacy of loaded bioactive molecules. Nevertheless, the clinical translation of LCN-based carriers has been slow. In this review, we highlight recent advances and challenges in the development and application of LCN, providing examples of their topical, oral, and intravenous drug delivery applications, and discussing translational obstacles to LCN as a NP technology.