Spherical Bilayer Research Articles

Influence of Lipid Composition, pH, and Temperature on Physicochemical Properties of Liposomes with Curcumin as Model Drug.

The physicochemical properties of large unilamellar vesicles (LUVs) were assessed with respect to lipid composition, pH, time, and temperature by monitoring their size, zeta potential, drug payload, and thermal behavior. A conventional thin film hydration technique was employed to prepare liposomes from soy phosphatidylcholine (SPC), dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG), and a 7:3 (M/M) mixture of DPPC+DPPG along with 30 mole% cholesterol in each combination. While the size of liposomes depended on lipid composition, pH and temperature, the zeta potential was found to be independent of the pH of the medium, although it varied with liposome type. Spherical morphology and bilayer were observed by electron microscopy. The phase transition temperature increased with decreasing pH. Membrane micro-viscosity showed the highest value for SPC, and membrane rigidity increased with increasing pH. The entrapment efficiency of liposomes with reference to curcumin was as follows: DPPC>DPPC+DPPG>DPPG>SPC. Sustained release of curcumin was observed for all liposomes. Curcumin-loaded liposomes exhibited substantial antibacterial activity against the gram-positive bacteria Bacillus amyloliquefaciens. Additional studies are needed to improve the understanding of the effect of formulation variables on the physicochemical stability of liposomes.

CO₂-Responsive Pillar[5]arene-Based Molecular Recognition in Water: Establishment and Application in Gas-Controlled Self-Assembly and Release.

Here we developed a novel CO2-responsive pillararene-based molecular recognition motif established from a water-soluble pillar[5]arene and an anionic surfactant, sodium dodecyl sulfonate (SDS). The inclusion complex acted as a supramolecular amphiphile and self-assembled into spherical bilayer vesicles as confirmed by DLS, SEM, and TEM experiments. These vesicles were disrupted upon bubbling N2 or adding much more SDS to eliminate the inclusion complex. The assembly and disassembly of vesicles were successfully employed in gas and surfactant triggered releases of calcein, a water-soluble dye.

Effect of Erythrodiol, A Natural Pentacyclic Triterpene from Olive Oil, on the Lipid Membrane Properties.

The effect of erythrodiol, a natural pentacyclic triterpene to which humans are exposed through nutrients, on the lipid membranes is studied using liposomes as a membrane model. Empty and erythrodiol-loaded liposomes were prepared by the reverse phase evaporation method followed by the extrusion and by the thin film hydration method. Liposomes were characterized in terms of size and zeta potential and were imaged by transmission electron microscopy (TEM) and atomic force microscopy (AFM). The effect of erythrodiol on thermotropic behavior of DPPC bilayers is also examined by differential scanning calorimetry (DSC). The DSC thermograms suggested that erythrodiol interacted with the polar head groups of phospholipids and may produce a disruption of the ordering of the alkyl chains. The diffraction light scattering analysis showed that erythrodiol-loaded liposomes presented a decrease in the vesicle size when compared to blank liposomes. Images obtained by TEM confirmed the formation of unilamellar and spherical liposomes. AFM images showed spherical vesicles and single lipid bilayers. The latter were more abundant in the preparations containing erythrodiol than in the blank ones. Moreover, erythrodiol-loaded liposomes tended to rupture into single lipid bilayers during scanning. The study may provide a better understanding of pentacyclic triterpenes-membrane interaction.

Competitive Geometric Evolution of Amphiphilic Interfaces

We derive the curvature driven flow of closed-loop pore structures which arise in quasi-stationary states in the $H^{-1}$ gradient flow of the weakly functionalized Cahn--Hilliard free energy which models amphiphilic mixtures. We extend this result to a sharp-interface reduction for the competitive evolution of disjoint collections of bilayer interfaces and closed-loop pores. In particular, for a mixture of spherical bilayers and circular closed pores we explicitly identify two regimes: one in which spherical bilayers extinguish and the circular pores arrive at a common radius, and a complimentary regime in which spherical bilayers of differing radii stably coexist with common-radius, closed-loop, circular pores.

Centerband-only-detection-of-exchange (31)P nuclear magnetic resonance and phospholipid lateral diffusion: theory, simulation and experiment.

Centerband-only-detection-of-exchange (CODEX) (31)P NMR lateral diffusion measurements were performed on dimyristoylphosphatidylcholine (DMPC) assembled into large unilamellar spherical vesicles. Optimization of sample and NMR acquisition conditions provided significant sensitivity enhancements relative to an earlier first report (Q. Saleem, A. Lai, H. Morales, and P. M. Macdonald, Chem. Phys. Lipids, 2012, 165, 721). An analytical description was developed that permitted the extraction of lateral diffusion coefficients from CODEX data, based on a Gaussian-diffusion-on-a-sphere model (A. Ghosh, J. Samuel, and S. Sinha, Europhys. Lett., 2012, 98, 30003-p1) as relevant to CODEX (31)P NMR measurements on a population of spherical unilamellar phospholipid bilayer vesicles displaying a distribution of vesicle radii.

Interlayer Coupling Effect on Buckling Modes of Spherical Bilayers

AbstractThis study examined the critical buckling characteristics of hydrostatically pressurized double-walled complete spherical shells. An analytical model based on small deflection thin shell theory is presented; the equations are solved in conjunction with variational principles. Axisymmetric and inextensional assumptions are not initially used in the exact formulation. This approach therefore avoids any discussion about the validity of the solution and allows the model to be extended to cover more generic nonaxisymmetric cases with relative ease. The analytical results are presented using illustrative buckling modes. Based on the developed formulation, only axisymmetric eigenmodes were found to occur despite the inclusion of the effect of interactions between outer and inner shells. Critical modes that are symmetric or antisymmetric about the equator may be determined depending on the combination of the stiffness connecting the outer and inner shells and the radius-to-wall thickness ratios.

Spontaneous unilamellar polymer vesicles in aqueous solution

A unilamellar polymeric vesicle is a self-assembled structure of a block copolymer that forms a spherical single bilayer structure with a hydrophobic interlayer and a hydrophilic surface. Due to their enhanced colloidal stability and mechanical property, controllable surface functionality, or tunable membrane thickness, polymeric vesicles are useful in nano and bio-science, providing potential applications as nanosized carriers for catalysts, drugs, and enzymes. For fabrication of a unilamellar vesicle, however, preparative procedures with a few steps are inherently required. Herein, without complicated preparative procedures, we report spontaneous unilamellar polymeric vesicles with nanometer sizes (<100 nm), which are prepared by simply mixing a triblock copolymer, Pluronic P85 (PEO26PPO40PEO26), and an organic derivative, 5-methyl salicylic acid (5mS), in aqueous solution. Depending on the 5mS concentration and the temperature, the P85-5mS mixtures presented various self-assembled nanostructures such as spherical and cylindrical micelles or vesicles, which were characterized by small angle neutron scattering and cryo-TEM, resulting in a phase diagram drawn as a function of temperature and the 5mS concentration. Interestingly the critical temperature for the micelle-to-vesicle phase transition was easily controlled by varying the 5mS concentration, i.e. it was decreased with increasing the 5mS concentration.

EPR Spectroscopy of MOLB2C2-A Reveals Mechanism of Transport for A Type II Molybdate Importer

ABC importers are embedded in the plasma membrane of all bacteria. There they facilitate the uptake of several vital nutrients and cofactors. Due to differences in structure and activity, ABC importers are divided into two types. Type I importers have been well studied, but most of what we know about Type II importers has been observed in studies of the vitamin B12 importer, BtuC2D2. MolB2C2 (formally known as HI1470/71) is also a Type II importer, but its substrate, molybdate, is about 10x smaller than vitamin B12. To understand mechanistic differences among Type II importers, we focused our studies on MolBC where alternative conformations may be required to transport its relatively small substrate. To investigate the mechanism of MolBC, we employed electron paramagnetic resonance (EPR) spectroscopy with the transporter imbedded in detergent micelles and liposomes (spherical lipid bilayers). The use of both detergent and lipid have allowed us to identify conformational changes in MolBC and the impact of the lipid environment. We observed that nucleotide binding and hydrolysis shift the conformation of MolBC at both the cytoplasmic and periplasmic gates. Mechanistic differences between MolBC and other Type II transporters highlight potential effects of substrate size on transport. Combining our results, we propose a mechanism for MolBC-A embedded in a lipid bilayer, which gives new insight in the transport of small substrates.

Pore-forming Compounds as Signal Transduction Elements for Highly Sensitive Biosensing

Pore-forming compounds are attracting much attention due to the signal transduction ability for the development of highly sensitive biosensing. In this review, we describe an overview of the recent advances made by our group in the design of molecular sensing interfaces of spherical and planar lipid bilayers and natural bilayers. The potential uses of pore-forming compounds, such as gramicidin and MCM-41, in lipid bilayers and natural glutamate receptor channels in biomembrane are presented.

Superhydrogels of Nanotubes Capable of Capturing Heavy‐Metal Ions

Self-assembly regulated by hydrogen bonds was successfully achieved in the system of lithocholic acid (LCA) mixed with three organic amines, ethanolamine (EA), diethanolamine (DEA), and triethanolamine (TEA), in aqueous solutions. The mixtures of DEA/LCA exhibit supergelation capability and the hydrogels consist of plenty of network nanotubes with uniform diameters of about 60 nm determined by cryogenic TEM. Interestingly, the sample with the same concentration in a system of EA and LCA is a birefringent solution, in which spherical vesicles and can be transformed into nanotubes as the amount of LCA increases. The formation of hydrogels could be driven by the delicate balance of diverse noncovalent interactions, including electrostatic interactions, hydrophobic interactions, steric effects, van der Waals forces, and mainly hydrogen bonds. The mechanism of self-assembly from spherical bilayer vesicles into nanotubes was proposed. The dried hydrogels with nanotubes were explored to exhibit the excellent capability for capturing heavy-metal ions, for example, Cu(2+), Co(2+), Ni(2+), Pb(2+), and Hg(2+). The superhydrogels of nanotubes from the self-assembly of low-molecular-weight gelators mainly regulated by hydrogen bonds used for the removal of heavy-metal ions is simple, green, and high efficiency, and provide a strategic approach to removing heavy-metal ions from industrial sewage.

Creation of Cross-Linked Bilayer Membranes That Can Incorporate Membrane Proteins from Oligo-Asp-Based Peptide Gemini Surfactants

We designed novel bilayer-forming amphiphiles based on the cyclic oligo-Asp-based peptide gemini (PG) surfactants cr-D2C12 and cr-D3C12, which consist of -Cys(Asp)nCys- (n = 2 or 3) as a core peptide and two Cys residues containing a dodecylamidomethyl group. Dynamic light scattering and transmission electron microscopy measurements revealed the formation of spherical bilayer membranes that could incorporate the light-harvesting antenna complex 2 (LH2) from Rhodopseudomonas acidophila . Furthermore, this proteoliposome-like conjugate could be assembled onto cationized glass and mica to form planar bilayer membranes incorporating LH2. Using atomic force microscopy, we observed LH2 protruding (ca. 1.2-1.5 nm) from flat terraces of the planar bilayer membranes formed from cr-D2C12 or cr-D3C12. Thus, our designed PG surfactants are a new class of bilayer-forming amphiphiles that may be applied to the study of various membrane proteins.

Correlation between composition of the outer layer and phase asymmetry for vesicles ruptured by phospholipase D.

Spherical phospholipid bilayers, vesicles, were prepared by using the layer-by-layer double emulsion technique, which allows individual layers to be formed asymmetrically. Phases of the layers were adjusted by selecting the lipid tail group. The head group composition of the vesicle outer layer varied 0-100% of phosphatidylcholine (PC) by 10% under the condition that the diameter of the vesicle was kept constant. On the outer layer of the vesicle, the phospholipase D (PLD) reacted to convert PC to phosphatidic acid. The reaction induced a curvature change of the vesicles, which eventually led them to rupture. Response time from the PLD injection to the rupture was measured against the different compositions of the outer layer at each phase (solid and liquid) using the fluorescence intensity change of pH-sensitive dye encapsulated in the vesicles. From this measurement, the rupture caused by the PLD reaction was analyzed with respect to the phase asymmetry of the layers and the composition of the outer layer. These results were interpreted with the lipid density and stability of the layers. It was observed that the solid phase of the outer layer had a variance in response time according to the phase of the inner layer, whereas the liquid phase did not. Additionally, the response of the solid phase of the outer layer at the liquid phase of the inner layer was faster than at the solid phase of the inner layer as a result of its stability.

RETRACTED ARTICLE:Effect of Mixed-Phospholipid Layer on Phospholipase D Reaction-induced Vesicle Rupture

Spherical phospholipid bilayers, or vesicles, were prepared layer by layer using a double-emulsion technique, which allows the outer layer of the vesicles to be formed with two phospholipids that have different head groups: phosphatidylcholine (PC) and phosphatidylethanolamine. At the outer layer of the vesicles, the phospholipase D (PLD) catalyzed for the conversion of PC to phosphatidic acid. The reaction caused by PLD induced the curvature change of the vesicles, which eventually led to the rupture of the vesicles. Before the investigation, the ratio of dioleoylphosphatidylethanolamine to oleoylhydroxyphosphatidylethanolamine was found as a condition such that the vesicles made with the mixed lipids were as stable as those made with pure dioleoylphosphatidylcholine. Response time from the PLD injection to vesicle rupture was monitored by the composition of the outer layer by the fluorescence intensity change of pH-sensitive dye encapsulated in the vesicles. The response time began to be slowed at approximately 30% PC. The response times for the compositions were associated with the surface density of PC at the outer layer. These results also seem to be determined by the size of PLD, specifically the PLD active site.

Effect of Phospholipid Bilayer Phase Asymmetry on Phospholipase D Reaction-Induced Vesicle Rupture

Spherical phospholipid bilayers, vesicles, were formed with respect to phase of each layer via a double emulsion technique. At the outer layer of the vesicles, phospholipase D catalyzed for the conversion of phosphatidylcholine (PC) to phosphatidic acid (PA). The reaction caused by phospholipase D (PLD) induced a curvature change in the vesicles, which eventually led them to rupture. Response time from the PLD injection to the rupture was monitored for the phase of each layer by using fluorescence intensity changes of pH-sensitive dye encapsulated in the vesicles. It was found that low ionic strength and asymmetric phase retarded response time. The retardation seems to be related to the stability of the vesicles, which is due to the interaction between the lipid molecules. In the liquid phases of the outer lipid layers, the unexpected slow response time may be attributed either to the fast lateral diffusion, which relieves the curvature change of the vesicles, or to the low concentration of PCs, which are less for the reaction compared to the solid phase of the outer lipid layer, rather than the stability.

Asymmetric distribution of cone-shaped lipids in a highly curved bilayer revealed by asmall angle neutron scattering technique

We have investigated the lipid sorting in a binary small unilamellar vesicle (SUV)composed of cone-shaped (1,2-dihexanoyl-sn-glycero-3-phosphocholine: DHPC) andcylinder-shaped (1,2-dipalmitoyl-sn-glycero-3-phosphocholine: DPPC) lipids. In order toreveal the lipid sorting we adopted a contrast matching technique of small angle neutronscattering (SANS), which extracts the distribution of deuterated lipids in the bilayerquantitatively without steric modification of lipids as in fluorescence probe techniques.First the SANS profile of protonated SUVs at a film contrast condition showed that SUVshave a spherical shape with an inner radius of 190 Å and a bilayer thickness of 40 Å. The SANSprofile of deuterated SUVs at a contrast matching condition showed a characteristicscattering profile, indicating an asymmetric distribution of cone-shaped lipids in thebilayer. The characteristic profile was described well by a spherical bilayer model.The fitting revealed that most DHPC molecules are localized in the outer leaflet.Thus the shape of the lipid is strongly coupled with the membrane curvature.We compared the obtained asymmetric distribution of the cone-shaped lipids inthe bilayer with the theoretical prediction based on the curvature energy model.

Elastic energy of polyhedral bilayer vesicles

In recent experiments [M. Dubois, B. Demé, T. Gulik-Krzywicki, J.-C. Dedieu, C. Vautrin, S. Désert, E. Perez, and T. Zemb, Nature (London) 411, 672 (2001)] the spontaneous formation of hollow bilayer vesicles with polyhedral symmetry has been observed. On the basis of the experimental phenomenology it was suggested [M. Dubois, V. Lizunov, A. Meister, T. Gulik-Krzywicki, J. M. Verbavatz, E. Perez, J. Zimmerberg, and T. Zemb, Proc. Natl. Acad. Sci. USA 101, 15082 (2004)] that the mechanism for the formation of bilayer polyhedra is minimization of elastic bending energy. Motivated by these experiments, we study the elastic bending energy of polyhedral bilayer vesicles. In agreement with experiments, and provided that excess amphiphiles exhibiting spontaneous curvature are present in sufficient quantity, we find that polyhedral bilayer vesicles can indeed be energetically favorable compared to spherical bilayer vesicles. Consistent with experimental observations we also find that the bending energy associated with the vertices of bilayer polyhedra can be locally reduced through the formation of pores. However, the stabilization of polyhedral bilayer vesicles over spherical bilayer vesicles relies crucially on molecular segregation of excess amphiphiles along the ridges rather than the vertices of bilayer polyhedra. Furthermore, our analysis implies that, contrary to what has been suggested on the basis of experiments, the icosahedron does not minimize elastic bending energy among arbitrary polyhedral shapes and sizes. Instead, we find that, for large polyhedron sizes, the snub dodecahedron and the snub cube both have lower total bending energies than the icosahedron.

Review of sunscreen and the emergence of non-conventional absorbers and their applications in ultraviolet protection

Protection against ultraviolet (UV) radiation is the major function of sunscreen lotions and UV-protective coatings for vehicles, homes, equipment and clothing. Sunscreen formulations have been optimized to become protective over a broader spectrum of UV radiation and maintain greater photostability. They are comprised of organic and inorganic components that act as chemical and physical UV protectors, respectively. Some of the organic components are limited by their spectrum of protection and photostability. Studies using solid lipid nanoparticles, recently explored organic molecules, inorganic components and antioxidants attempt to further optimize UV protection. In this review, we examine traditional and emerging nanoparticle components and highlight novel ideas in UV protection which may provide pathways for future studies.

Minimal bending energies of bilayer polyhedra.

Motivated by recent experiments on bilayer polyhedra composed of amphiphilic molecules, we study the elastic bending energies of bilayer vesicles forming polyhedral shapes. Allowing for segregation of excess amphiphiles along the ridges of polyhedra, we find that bilayer polyhedra can indeed have lower bending energies than spherical bilayer vesicles. However, our analysis also implies that, contrary to what has been suggested on the basis of experiments, the snub dodecahedron, rather than the icosahedron, generally represents the energetically favorable shape of bilayer polyhedra.

Solution-processed bulk heterojunction photovoltaic devices based on poly(2-methoxy,5-octoxy)-1,4-phenylenevinylene-multiwalled carbon nanotubes/PbSe quantum dots bilayer

A solution-processed bulk heterojuction photovoltaic cell was fabricated based on poly[(2-methoxy,5-octoxy)-1,4-phenylenevinylene](MOPPV)-multiwalled carbon nanotubes (MWNT)/spherical PbSe quantum dots bilayer. Surface morphology shows the interpenetrating network of well-dispersed MWNT in MOPPV matrix. Blueshifted band in absorption and photoluminescence spectra indicate the strong electron interaction between MWNT and MOPPV. A marked twofold increase in short-circuit current (1.71 mA/cm2) and power-conversion efficiency (0.40%) of ITO/MOPPV-MWNT:phenyl-C61-butyric acid methyl ester (PCBM)/PbSe/Al devices was achieved compared with that without MWNT. Results indicate that the enhanced performance was contributed by high photocurrent due to efficient exciton dissociation, charge transfer, and mobility in MWNT pathway.

Liposomes in dermatology today

Liposomes are vesicles consisting of spherical phospholipid bi-layers with specific properties making them useful for topical application of drugs. Liposome research has expanded considerably over the last 30 years and nowadays, it is possible to construct a wide range of liposomes varying in size, phospholipids composition and surface characteristics to suit the specific application for which they are intended. In dermatology, the topical application of liposomes has proven to be of therapeutic value. Liposomes can be used as carriers for hydrophilic as well as lipophilic therapeutic agents because of their amphipathic character. They may improve stabilization of instable drugs by encapsulating them and serve as penetration enhancers facilitating the transport of compounds that otherwise cannot penetrate the skin. Liposomes help in reducing skin irritation by sustaining the release of drugs and by hydration of the epidermis. They also have the potential to target drugs into the pilosebaceous structures and hence they have an additional advantage for treatment of hair follicle-associated disorders. Clinical data indicate that 5-ALA encapsulated in liposomes improves the quality of Fluorescence Diagnosis by ALA-induced Porphyrins (FD) and optimizes the results of Photodynamic Therapy (PDT).