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Vorticity banding in rodlike virus suspensions.

Vorticity banding under steady shear flow is observed in a suspension of semiflexible colloidal rods (fd virus particles) within a part of the paranematic-nematic biphasic region. Banding occurs uniformly throughout the cell gap within a shear-rate interval (.gamma-, .gamma+) , which depends on the fd concentration. For shear rates below the lower-border shear rate .gamma- only shear elongation of inhomogeneities, which are formed due to paranematic-nematic phase separation, is observed. Within a small region just above the upper-border shear rate .gamma+ , banding occurs heterogeneously. An essential difference in the kinetics of vorticity banding is observed, depending on the morphology of inhomogeneities formed during the initial stages of the paranematic-nematic phase separation. Particle tracking and polarization experiments indicate that the vorticity bands are in a weak rolling flow, superimposed on the applied shear flow. We propose a mechanism for the origin of the banding instability and the transient stability of the banded states. This mechanism is related to the normal stresses generated by inhomogeneities formed due to the underlying paranematic-nematic phase transition.

Journal Article↗

Spin label studies on rat liver and heart plasma membranes: effects of temperature, calcium, and lanthanum on membrane fluidity.

The structures of rat liver and heart plasma membranes were studied with the 5-nitroxide stearic acid spin probe, I(12,3). The polarity-corrected order parameters (S) of liver and heart plasma membranes were independent of probe concentration only if experimentally determined low I(12,3)/lipid ratios were employed. At higher probe/lipid ratios, the order parameters of both membrane systems decreased with increasing probe concentration, and these effects were attributed to enhanced nitroxide radical interactions. Examination of the temperature dependence of approximate and polarity-corrected order parameters indicated that lipid phase separations occur in liver (between 19 degrees and 28 degrees C) and heart (between 21 degrees and 32 degrees C) plasma membranes. The possibility that a wide variety of membrane-associated functions may be influenced by these thermotropic phase separations is considered. Addition of 3.9 mM CaCl2 to I(12,3)-labeled liver plasma membrane decreased the fluidity as indicated by a 5% increase in S at 37 degrees C. Similarly, titrating I(12,3)-labeled heart plasma membranes with either CaCl2 or LaCl3 decreased the lipid fluidity at 37 degrees C, although the magnitude of the La3+ effect was larger and occurred at lower concentrations than that induced by Ca2+; addition of 0.2 mM La3+ or 3.2 mM Ca2+ increased S by approximately 7% and 5%, respectively. The above cation effects reflected only alterations in the membrane fluidity and were not due to changes in probe--probe interactions. Ca2+ and La3+ at these concentrations decrease the activities of such plasma membrane enzymes as Na+, K+-ATPase and adenylyl cyclase, and it is suggested that the inhibition of these enzymes may be due in part to cation-mediated decreases in the lipid fluidity.

Animals↗

Studies on the damage to Escherichia coli cell membrane caused by different rates of freeze-thawing.

Freeze-thawing of Escherichia coli cells caused a release of cell membrane components such as protein, phospholipids and lipopolysaccharides. A greater amount of release and a lesser extent of cell survival were seen in slow freeze-thawing than in rapid freeze-thawing. Several dehydrogenases in the cells were also freed. The mode of release was also dependent on the rate of freeze-thawing. The materials released by slow freeze-thawing were found to be mostly composed of outer membrane components, whereas the materials released by rapid freeze-thawing contained cytoplasmic as well as outer membrane components. The chemical composition of these fragments differed significantly from that of the original membranes. The relative content of cytoplasmic membrane-bound enzymes in these fragments also differed from that of the cytoplasmic membrane. The fragmentation was assumed to have resulted mainly from the crystallization of external water. In slow fraeeze-thawing, it was considered that the phase separation of the membrane phospholipid bilayer increased the possibility of outer membrane fragmentation. Rapid freeze-thawing caused cytoplasmic membrane damage to the cells as well as to the outer membrane. In rapid freeze-thawing, the effect of phase separation appeared to be small because of rapid passage through the transition temperatures. The presence of 10% glycerol completely inhibited the release of cellular materials and enzymes. Cell survival was maintained at a high level in the glycerol-treated samples whether freeze-thawed slowly or rapidly.

Cell Membrane↗

Interaction of polyethyleneglycol-phospholipid conjugates with cholesterol-phosphatidylcholine mixtures: sterically stabilized liposome formulations.

PURPOSE: The purpose of this study was to investigate polyethyleneglycol (PEG)-phosphatidylethanolamine (PE) conjugate interaction with cholesterol-phospholipid mixtures in an attempt to explain the effect of cholesterol on liposome circulation time. METHODS: Differential scanning calorimetry, NMR, electron microscopy, dynamic light scattering and fluorescence spectroscopy were the major methods used. RESULTS: Studies performed in the absence of cholesterol indicated the formation of three distinct physical states depending on the chain length of PEG in PEG-PE. Mixed micelle formation was observed at concentrations of PEG(1,000)-DPPE above 7 mol-% of lipid. Phase separated lamellae were observed at all concentrations of PEG( 12,000)-DPPE (Bedu-Addo et al. Pharm. Res. 13:710-717 (1996)). Upon incorporation of high concentrations of cholesterol >30 mol% into the lipid bilayer, the formation of phase separated lamellae was completely inhibited and the formation of mixed micelles significantly reduced. At high concentrations of PEG(1,000)-PE, solubilization of the bilayer occurred with preferential solubilization of cholesterol over phosphatidylcholine. Maximum steric stabilization (surface protection) was observed with low concentrations of short chain PEG-PE and high concentrations of cholesterol. CONCLUSIONS: The study provides a physical mechanism for the following observations: the blood circulation time is significantly increased or decreased with liposomes highly enriched with cholesterol or PEG-PE respectively.

Calorimetry, Differential Scanning↗

Effects of prostaglandin E2 and progesterone on rat brain synaptosomal plasma membranes.

The lipid fluidity of rat brain synaptosomal plasma membranes (SPM) labelled with 1,6-diphenyl-1,3,5-hexatriene (DPH) was increased by prostaglandin E2 (PGE2) and decreased by progesterone, as indicated by steady-state fluorescence anisotropy [(ro/r)-1]-1. Arrhenius-type plots of [(ro/r)-1]-1 indicated a lipid phase separation of SPM at approximately 23.5 degrees C which was reduced to approximately 18.1 degrees C by PGE2 and increased to approximately 34.6 degrees C by progesterone. Treatment of SPM by PGE2 and progesterone caused an increase of the lipid phase separation to approximately 32.4 degrees C. Arrhenius plots of Na+/K(+)-ATPase activity in control SPM exhibited a break point at approximately 23.1 degrees C which was reduced to approximately 17.8 degrees C by PGE2 and increased to approximately 32.6 degrees C by progesterone. SPM treated with PGE2 plus progesterone showed an increased break point at approximately 29.3 degrees C. Na+/K(+)-ATPase activity was increased at a PGE2 concentration range between 0.1 and 3 microM; higher concentrations (up to 10 microM) led to a gradual inhibition of enzyme activity. Progesterone (0.1-10 microM) and PGE2 plus progesterone both produced a gradual decrease in enzyme activity. The allosteric inhibition of Na+/K(+)-ATPase by fluoride (F-) (as reflected by changes in the Hill coefficient) was modulated by PGE2 and progesterone. The perturbations of membrane lipid structure and changes in membrane fluidity provide a basis for suggesting an independent non-genomic mechanism for the progesterone-induced alterations in the effects of PGE2 on brain function.

Animals↗

Modulation of particulate nitric oxide synthase activity and peroxynitrite synthesis in cholesterol enriched endothelial cell membranes.

Endothelium-derived relaxing factor/nitric oxide (EDRF/NO) is produced by the vascular wall and is a key modulator of vascular tone and blood pressure. Since reduced EDRF/NO release from the endothelium is a major key event in the development of atherosclerosis, we investigated the effect of cholesterol on endothelial cell particulate (membrane-bound) NO synthase activity. Low concentrations (up to 0.2 mM) of liposomal cholesterol progressively activated plasma membrane-bound NO synthase. Increasing cholesterol concentration above that which maximally stimulated enzyme activity produced a progressive inhibition with respect to the control value. In time course experiments using endothelial cell plasma membranes enriched with cholesterol, changes in NO production were followed by analogous changes in soluble guanylate cyclase activity (sGC). N-Monomethyl-L-arginine (L-NMMA) (1 mM) inhibited particulate NO synthase activity at all cholesterol concentrations used with subsequent decreases in cGMP production. Egg lecithin liposomes (free of cholesterol) had no effect on NO synthase activity. A three-fold increase in superoxide (O2-) and a 2.5-fold increase in NO formation followed by an eight-fold increase in peroxynitrite (ONOO-) production by cholesterol-treated microsomes isolated from endothelial cells was observed, one which rose further up to eight-fold in the presence of superoxide dismutase (SOD) (10 U/mL). Cholesterol had no effect on Lubrol-PX solubilized membrane-bound NO synthase or on cytosolic (soluble) NO synthase activities of endothelial cells. Cholesterol modulated lipid fluidity of plasma membranes labelled with 1,6-diphenyl-1,3,5-hexatriene (DPH) as indicated by the steady state fluorescence anisotropy [(ro/r)-1]-1. Arrhenius plots of [(ro/r)-1]-1 indicated that the lipid phase separation of the membranes at 26.2 +/- 1.5 degrees was elevated to 34.4 +/- 1.9 degrees in cholesterol-enriched membranes, consistent with a general decrease in membrane fluidity. Cholesterol-enriched plasma membranes treated with egg lecithin liposomes showed a lipid phase separation at 27.5 +/- 1.6 degrees, indicating the reversible effect of cholesterol on membrane lipid fluidity. Arrhenius plots of NO synthase activity exhibited break point at 26.9 +/- 1.8 degrees which rose to 35.6 +/- 2.1 degrees in 0.5 mM cholesterol-treated plasma membranes and decreased to 21.5 +/- 1.4 degrees in plasma membranes treated with 0.2 mM cholesterol. The allosteric properties of plasma membrane-bound NO synthase inhibited by Mn2+ (as reflected by changes in the Hill coefficient) were changed by cholesterol, consistent with modulations of the fluidity of the lipid microenvironment of the enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Oxidoreductases↗

Biomaterial films of Bombyx mori silk fibroin with poly(ethylene oxide).

Phase separation into controllable patterned microstructures was observed for Bombyx mori silkworm silk and poly(ethylene oxide) (PEO) (900000 g/mol) blends cast from solution. The evolution of the microstructures with increasing PEO volume fraction is strikingly similar to the progression of phases and microstructures observed with surfactants. The chemically patterned materials obtained provide engineerable biomaterial surfaces with predictable microscale features which can be used to create topographically patterned or chemically functionalized biomaterials. Solution blending was used to incorporate water-soluble PEO into silk to enhance elasticity and hydrophilicity. The sizes of the globule fibroin phase ranged from 2.1 +/- 0.5 to 18.2 +/- 2.1 microm depending on the ratio of silk/PEO. Optical microscopy and SEM analysis confirmed the micro-phase separation between PEO and silk. Surface properties were determined by XPS and contact angle. Methanol can be used to control the conformational transition of silk fibroin to the insoluble beta-sheet state. Subsequentially, the PEO can be easily extracted from the films with water to generate silk matrixes with definable porosity and enhanced surface roughness. These blend films formed from two biocompatible polymers provide potential new biomaterials for tissue engineering scaffolds.

Animals↗

Phase behavior of amorphous molecular dispersions I: Determination of the degree and mechanism of solid solubility.

PURPOSE: To understand the phase behavior and the degree and mechanism of the solid solubility in amorphous molecular dispersions by the use of thermal analysis. METHODS: Amorphous molecular dispersions of trehalose-dextran and trehalose-PVP were prepared by co-lyophilization. The mixtures were exposed to 23 degrees C, 40 degrees C, and 50 degrees C [75% relative humidity (RH)] and 23 degrees C (69% RH) storage conditions, respectively. Thermal analysis was conducted by modulated differential scanning calorimeter (MDSC). RESULTS: Upon exposure to moisture, two glass transition temperatures (TgS), one for phase-separated amorphous trehalose (Tg1) and the other for polymer-trehalose mixture (Tg2), were observed. With time, Tg2 increased and reached to a plateau (Tg(eq)), whereas Tg1 disappeared. The disappearance of Tg1 was attributed to crystallization of the phase-separated amorphous trehalose. It was observed that Tg(eq) was always less than Tg of pure polymer. The lower Tg(eq) when compared to Tg of pure polymer may be the result of solubility of a fraction of trehalose in the polymers chosen. The miscible fraction of trehalose was estimated to be 12% and 18% wt/wt in dextran at 50 degrees C/75% RH and 23 degrees C/75% RH, respectively, and 10% wt/wt in PVP at 23 degrees C/69% RH. CONCLUSIONS: Mixing behavior of trehalose-dextran and trehalose-PVP dispersions were examined both experimentally and theoretically. A method determining the "extent of molecular miscibility," referred to as "solid solubility," was developed and mechanistically and thermodynamically analyzed. Solid dispersions prepared at trehalose concentrations below the "solid solubility limit" were physically stable even under accelerated stability conditions.

Calorimetry, Differential Scanning↗

Simulation and theory of self-assembly and network formation in reversibly cross-linked equilibrium polymers.

A simulation model of hard spheres capable of reversible assembly into chains, which then may reversibly cross-link into networks, has been studied through grand canonical Monte Carlo simulation. Effects of varying intra- and interchain bond strengths, chain flexibilities, and restrictions on cross-linking angle were investigated. Observations including chain-length distributions and phase separation could be captured in most cases using a simple model theory. The coupling of chain growth to cross-linking was shown to be highly sensitive to the treatment of cross-linking by chain ends. In some systems, ladderlike domains of several cross-links joining two chains were common, resulting from cooperativity in the cross-linking. Extended to account for this phenomenon, the model theory predicts that such cooperativity will suppress phase separation in weakly polymerizing chains and at high cross-link concentration. In the present model, cross-linking stabilizes the isotropic phase with respect to the nematic phase, causing a shift in the isotropic-nematic transition to higher monomer concentration than in simple equilibrium polymers.

Computer Simulation↗

Presence of the complement-regulatory protein membrane cofactor protein (MCP, CD46) as a membrane-associated product in seminal plasma.

The seminal plasma complement regulator membrane cofactor protein (MCP) was examined by sequential centrifugation and phase separation in the detergent Triton X-114. The presence of MCP components in seminal plasma depleted of the 40 kDa sperm MCP product by low speed centrifugation was confirmed. Subsequent centrifugation at 2200 g recovered a pellet containing a prominent 60 kDa and a weak 50-55 kDa MCP component. A 60 kDa MCP product remained detectable in the supernatant fraction after this centrifugation step but this was depleted by ultracentrifugation. Recovery of the seminal plasma MCP components in the pellet fraction obtained by ultracentrifugation suggested that seminal plasma MCP is membrane-associated. Seminal plasma fractions were also subjected to phase separation in Triton X-114. MCP components in both pellet and supernatant fractions partitioned to the detergent phase, confirming that seminal plasma MCP is membrane associated. The origin of these proteins was investigated by analysing MCP products in seminal plasma from vasectomized men. The 40 kDa sperm MCP protein was absent but a 60 kDa MCP component, which partitioned to the detergent phase in Triton X-114, was evident. Seminal plasma therefore contains typical membrane-associated MCP products that appear to be derived distal to the ductus deferens.

Antigens, CD↗

Interactions of sugars with membranes.

Water profoundly affects the stability of biological membranes, and its removal leads to destructive events including fusion and liquid crystalline to gel phase transitions. In heterogeneous mixtures such as those found in biological membranes the phase transitions can lead to increases in permeability and lateral phase separations that often are irreparable. Certain sugars are capable of preventing these deleterious events by inhibiting fusion during drying and by maintaining the lipid in a fluid state in the absence of water. As a result, the increased permeability and lateral phase separations that accompany dehydration are absent. The weight of the evidence suggests strongly that there is a direct interaction between the sugars and lipids in the dry state. Although the evidence is less clear about whether these sugars can interact directly with hydrated bilayers, there are strong suggestions in the literature that sugars free in solution or covalently linked to membrane constituents can also affect the physical properties and presumably the stability of bilayers. Finally, we have far less evidence concerning the mechanism by which they do so, but the same sugars are also capable of preserving the structure and function of both membrane-bound and soluble proteins in the absence of water. We believe these effects may be important in the survival of intact cells and organisms such as seeds in the absence of water. Furthermore, in view of the practical importance of preserving biological structures we suspect that the results described here will ultimately have important applications in biology and medicine.

Animals↗

Use of a novel method for determination of partition coefficients to compare the effect of local anesthetics on membrane structure.

A new, simple procedure for the determination of partition coefficients (P) was developed based on spectral effects caused upon addition of solutes to spin labeled model lipid membranes, and on the knowledge of their water solubility. Values of P were determined for nine local anesthetics (LA), amino-esters and amino-amides. The results were in good agreement with those found by phase separation and by a more complex, previously reported, methodology (Lissi et al. (1990) Biochim. Biophys. Acta 1021, 46-50) applied to either EPR or fluorescence spectra of probes incorporated in the bilayers. Both the present and the previously reported procedures make use of effects on membrane structure evaluated by spectroscopic techniques and offer the advantage of not requiring phase separation. The spectral effects, indicative of a decrease in bilayer organization increased with LA concentration, reaching a maximum at the drug water solubility, indicating that partitioning in the membrane is limited by saturation of the aqueous phase. A thermodynamic analysis of the partition data according to Hill (Hill, M.W. (1974) Biochim. Biophys. Acta 356, 117-124) showed that the LAs did not display ideal behavior. Knowledge of the partition coefficients allowed a comparison between effects at the same drug concentration in the membrane. Within a given family (esters, acyclic amides, cyclic amides) no clear proportionality was observed between effect and LA hydrophobicity, as reflected in the partition coefficient. Rather, the membrane perturbing ability is a result of steric effects originating in the mismatch between anesthetic and phospholipid shapes.

Anesthetics, Local↗

Cholesterol bonded phase as a separation medium in liquid chromatography. Evaluation of properties and applications.

An extensive survey of the properties and separation capabilities of a cholesterol bonded phase is reported. The intermediate hydrophobic/hydrophilic properties of the bonded cholesterol material allows this stationary phase to be used for both reversed-phase and aqueous normal-phase separations. Interesting high selectivity is reported for the structural isomers of some antibiotics. The cholesterol bonded material does not display "phase collapse" in high aqueous content mobile phases. Variable temperature studies demonstrate that substantial structural changes of the bonded moiety occur that might be used to control selectivity. Finally, separation of some enantiomers of compounds with a variety of chemical structures is reported under reversed-phase conditions indicating that the cholesterol material may be chiral stationary phase with a broad range of applicability.

Anti-Bacterial Agents↗

Investigation of polylysine-dipalmitoylphosphatidylglycerol interactions in model membranes.

The effect of poly(L-lysine) on dipalmitoylphosphatidylglycerol bilayers has been studied by Raman and infrared spectroscopies, small-angle X-ray diffraction, and carboxyfluorescein escape experiments. The polypeptide is shown to induce a stabilization of the bilayer detected by the increase of interchain vibrational coupling and a slight decrease of the overall disorder. In addition, long polylysine (Mr 150,000) induces a positive shift of the gel to fluid transition temperature and, at lipid to lysine molar ratios greater than 1, a lateral phase separation within the bilayer. Raman and infrared spectra indicate modifications at the head group level. In contrast, short polylysine (Mr 4,000) leads to a decrease of the lipid thermotropic transition temperature, and no modification of the polar head group and no phase separation could be observed. These differences between short and long polypeptides are correlated with the conformation the polypeptide adopts upon binding to the lipid, which favors the formation of alpha-helices in the case of long polypeptides (Mr greater than or equal to 14,000). The X-ray data suggest that the basic polypeptide acts as a bridge between neighboring bilayers, thus causing their aggregation and dehydration.

Fluoresceins↗

Intermolecular hydrogen bonding between lipids: influence on organization and function of lipids in membranes.

Biological membranes have unique lipid compositions suggesting a specific role for many lipids. Evidence is reviewed concerning the intermolecular forces between glycero- and sphingolipids and cholesterol, the dependence of many of these interactions on the state of ionization of lipids, pH, ionic strength, and divalent cation concentration. The effect of intermolecular interactions between certain lipids on lipid clustering, interaction with cholesterol, on the conformation of proteins, and on transitions to the hexagonal phase is considered. Other forces which cause lipids phase separation or clustering are discussed. It is concluded that lipids are in dynamic equilibrium with their environment and can act as receptors for certain intra- or extra-cellular stimuli, which they can translate into a response by undergoing changes in fluidity, phase transitions, or phase separation.

Animals↗

Preparation of polylactic acid microcapsules containing ciprofloxacin.

Microcapsules have been used as drug delivery systems in the pharmaceutical field for sustained or controlled release of drug, and for artificial cells and organs. Biodegradable polymers, especially polylactic acid, have been widely used in this field. In this study, an attempt was made to develop a new method to prepare polylactic acid microcapsules for drug delivery. The biodegradable polylactic acid microcapsules were made by the phase separation process: two types of polylactic acid, poly[(D,L)lactic acid] and poly[(L)lactic acid] were combined as the membrane material. Because of the difference of the crystal properties of the two polymers, the aggregation which happens frequently in the phase separation process was prevented. As a model drug, Ciprofloxacin was encapsulated in the polylactic acid microcapsules.

Anti-Infective Agents↗

Purification and properties of a new polypeptide chain elongation factor, EF-1beta, from pig liver.

Eukaryotic polypeptide elongation factor 1 (EF-1) from pig liver has been resolved into two complementary factors, EF-1alpha and EF-1beta (Iwasaki, K., Mizumoto, K., Tanka, M., and Kaziro, Y. (1973) J. Biochem. (Tokyo) 74, 849). This paper describes the procedures for purification of EF-1beta and some properties of the purified factor. The purification method includes an aqueous two-phase separation technique, a treatment of the crude factor with sodium cholate and two successive column chromatographies on diethyl-aminoethyl-Sephadex A-50. By this method, EF-1beta was purified about 50-fold starting from the material obtained after two-phase separation followed by ammonium sulfate fractionation with a recovery of 20%. The purified EF-1beta appeared homogeneous, having a molecular weight of about 90,000. It consisted of two unequal subunits of the molecular weights of 55,000 and 30,000. It stimulates polymerization of phenylalanine dependent on poly(U) in the presence of both EF-1alpha and EF-2, as well as the EF-1alpha-dependent binding of phenylalanyl-tRNA to ribosomes in the presence of GTP. However, it had no effect on the stoichiometric binding of phenylalanyl-tRNA to ribosomes dependent on EF-1alpha in the presence of guanyl-5'-yl methylenediphosphonate. These results indicate that the function of EF-1beta is to stimulate the recycling of EF-1alpha.

Animals↗

Interactions of liposome bilayers composed of 1,2-diacyl-3-succinylglycerol with protons and divalent cations.

Bilayer liposomes were prepared by using pure DOSG (1,2-dioleoyl-3-succinylglycerol) or DPSG (1,2-dipalmitoyl-3-succinylglycerol) at pH 7.4 or above. These liposomes undergo destabilization upon incubation with acid. When calcein was used as an entrapped aqueous marker, half maximal content leakage was observed between pH 5.8-6.3. Differential scanning calorimetry showed that at pH 7.4, the chain-melting temperature (Tm) of DPSG was 60.4 degrees C, and increased with decreasing pH (Tm = 57.0 degrees C and 62.7 degrees C at pH 8.9 and 6.7, respectively). Below pH 6.7, extensive phase separation occurred as the major chain melting peak split into three peaks. These three peaks coalesced into one peak below pH 5. Freeze fracture electron micrographs of DOSG liposomes at pH 4 showed the formation of non-bilayer as well as hexagonal phase structures. The effects of divalent cations, such as Ca2+ and Mg2+, on the destabilization of DASG bilayers have also been studied. Differential scanning calorimetry studies of bilayers composed of DPSG showed that both Ca2+ and Mg2+ could increase the Tm of DPSG with increasing concentrations. However, under identical conditions Mg2+ was more effective than Ca2+ in increasing the Tm of DPSG. X-ray diffraction indicated that both Ca2+ and Mg2+ could induce DPSG bilayers to undergo a complete lamellar to hexagonal phase transition. There was a size-dependency on the plasma stability of DOSG liposomes. DOSG liposomes that were smaller in size were more stable in plasma than the larger ones. After incubation with plasma, DOSG liposomes became less acid-sensitive. DOSG immunoliposomes entrapping diphtheria toxin A chain were used as a model for cytoplasmic delivery of the novel pH-sensitive liposomes. The delivery activity was comparable to that of the conventional pH-sensitive liposomes containing unsaturated phosphatidylethanolamine. Our data indicate that the mechanism of liposome destabilization involves extensive bilayer phase separation as well as the formation of non-bilayer structures.

Calorimetry, Differential Scanning↗