Dipalmitoylphosphatidylcholine Model Research Articles

Dispersion of Hydrophilic Nanoparticles in Natural Rubber with Phospholipids

Coarse-grained molecular dynamics (CGMD) simulations were employed to investigate the effects of phospholipids on the aggregation of hydrophilic, modified carbon-nanoparticle fillers in cis-polyisoprene (cis-PI) composites. The MARTINI force field was applied to model dipalmitoylphosphatidylcholine (DPPC) lipids and hydrophilic modified fullerenes (HMFs). The simulations of DPPC in cis-PI composites show that the DPPC lipids self-assemble to form a reverse micelle in a rubber matrix. Moreover, HMF molecules readily aggregate into a cluster, in agreement with the previous studies. Interestingly, the mixture of the DPPC and HMF in the rubber matrix shows a cluster of HMF is encapsulated inside the DPPC reverse micelle. The HMF encapsulated micelles disperse well in the rubber matrix, and their sizes are dependent on the lipid concentration. Mechanical and thermal properties of the composites were analyzed by calculating the diffusion coefficients (D), bulk modulus (κ), and glass transition temperatures (Tg). The results suggest that DPPC acts as a plasticizer and enhances the flexibility of the HMF-DPPC rubber composites. These findings provide valuable insights into the design and process of high-performance rubber composites, offering improved mechanical and thermal properties for various applications.

The impact of physiologically relevant temperatures on physical properties of thylakoid membranes: a molecular dynamics study.

Thylakoid membranes are energy-converting membranes with a unique lipid composition. Though the membranes are primarily composed of proteins, their photosynthetic function is strongly influenced by the lipid constituents. Here we characterize, with molecular dynamics (MD) simulations, lipid bilayers with compositions representative of plant thylakoid membranes. We determine, in a wide range of temperatures, the physical parameters of the model membranes which are relevant for the photosynthetic function. We found a marked impact of temperature on membrane permeability due to a combination of increased compressibility and curvature of the membrane at elevated temperatures. With increasing temperatures, we observed increasingly smeared transmembrane density profiles of the membrane forming lipid headgroups predicting increased membrane flexibility. The diffusion coefficient of the lipids increased with temperature without apparent specificity for lipid species. Instead of a comprehensive experimental dataset in the relevant temperature range, we quantitatively compared and validated our MD results with MD simulations on a dipalmitoylphosphatidylcholine model system.

Asipimoksun DPPC Model Membranlar Üzerindeki Etkilerinin Kalorimetrik İncelenmesi

Liposomes or model membranes are widely used basic systems which mimic biological membranes. In this study, the physical interaction between dipalmitoyl phosphatidylcholine (DPPC) and the lipid-lowering drug acipimox was investigated using Differential Scanning Calorimetry (DSC) technique depending on different acipimox concentrations and temperature. The changes in the phase transition temperature, phase transition enthalpy and phase transition curve half-height width of the model membranes were taken into account. According to the DSC results, with the addition of acipimox into pure DPPC model membranes, the main phase transition temperature curve, which is around 41 °C, shifted to slightly higher temperatures, while the pre-transition temperature curve, which is around 35 °C, did not disappear. Moreover, increasing acipimox concentrations caused a slight broadening of the DSC thermograms of the model membrane DPPC. Since it is very important to understand the pharmacological activity of drugs in biomembranes, the investigation of the interaction between lipid-lowering drug acipimox and lipids may contribute to the biological effects of acipimox at the molecular level.

Ruscogenin interacts with DPPC and DPPG model membranes and increases the membrane fluidity: FTIR and DSC studies

Ruscogenin, a kind of steroid saponin, has been shown to have significant anti-oxidant, anti-inflammatory, and anti-thrombotic characteristics. Furthermore, it has the potential to be employed as a medicinal medication to treat a variety of acute and chronic disorders. The interaction of a drug molecule with cell membranes can help to elucidate its system-wide protective and therapeutic effects, and it's also important for its pharmacological activity. The molecular mechanism by which ruscogenin affects membrane architecture is still a mystery. Ruscogenin's interaction with zwitterionic dipalmitoyl phosphatidylcholine (DPPC) and anionic dipalmitoyl phosphatidylglycerol (DPPG) multilamellar vesicles (MLVs) was studied utilizing two non-invasive approaches, including: Fourier Transform Infrared (FTIR) spectroscopy and Differential Scanning Calorimetry. Ruscogenin caused considerable alterations in the phase transition profile, order, dynamics and hydration state of head groups and glycerol backbone of DPPC and DPPG MLVs at all concentrations. The DSC results indicated that the presence of ruscogenin decreased the main phase transition temperature (Tm) and enthalpy (ΔH) values of both membranes and increased half height width of the main transition (ΔT1/2). The FTIR results demonstrated that all concentrations (1, 3, 6, 9, 15, 24 and 30 mol percent) of ruscogenin disordered the DPPC MLVs both in the gel and liquid crystalline phases while it increased the order of DPPG MLVs in the liquid crystalline phase. Moreover, ruscogenin caused an increase in the dynamics of DPPC and DPPG MLVs in both phases. Additionally, it enhanced the hydration of the head groups of lipids and the surrounding water molecules implying ruscogenin to interact strongly with both zwitterionic and charged model membranes.

Effect of biphosphate salt on dipalmitoylphosphatidylcholine bilayer deformation by Tat polypeptide.

Translocation of positively charged cell penetrating peptides (CPP) through cell membrane is important in drug delivery. Here we report all-atom molecular dynamics simulations to investigate how a biphosphate salt in a solvent affects the interaction of a CPP, HIV-1 Tat peptide with model dipalmitoylphosphatidylcholine (DPPC) lipid bilayer. Tat peptide has a large number of basic arginines and a couple of polar glutamines. We observe that in absence of salt, the basic residues of the polypeptide get localized in the vicinity of the membrane without altering the bilayer properties much; polypeptide induce local thinning of the bilayer membrane at the area of localization. In presence of biphosphate salt, the basic residues, dressed by the biphosphate ions, are repelled by the phosphate head groups of the lipid molecules. However, polar glutamine prefers to stay in the vicinity of the bilayer. This leads to larger local bilayer thickness at the contact point by the polar residue and non-uniform bilayer thickness profile. The thickness deformation of bilayer structure disappears upon mutating the polar residue, suggesting importance of the polar residue in bilayer deformation. Our studies point to control bilayer deformation by appropriate peptide sequence and solvent conditions.

Probing of Interactions of Magnetite Nanoparticles Coated with Native and Aminated Starch with a DPPC Model Membrane.

Understanding the mechanism of interactions between magnetite nanoparticles and phospholipids that form cellular membranes at the molecular level is of crucial importance for their safe and effective application in medicine (e.g., magnetic resonance imaging, targeted drug delivery, and hyperthermia-based anticancer therapy). In these interactions, their surface coating plays a crucial role because even a small modification to its structure can cause significant changes to the behaviour of the magnetite nanoparticles that come in contact with a biomembrane. In this work, the influence of the magnetite nanoparticles functionalized with native and aminated starch on the thermodynamics, morphology, and dilatational elasticity of the model cell membranes was studied. The model cell membranes constituted the Langmuir monolayers formed at the air–water interface of dipalmitoylphosphatidylcholine (DPPC). The surface of the aminated starch-coated nanoparticles was enriched in highly reactive amino groups, which allowed more effective binding of drugs and biomolecules suitable for specific nano–bio applications. The studies indicated that the presence of these groups also reduced to some extent the disruptive effect of the magnetite nanoparticles on the model membranes and improved their adsorption.

Синтетические меротерпеноиды на основе терпеновых спиртов: синтез, самосборка и мембранотропные свойства

Currently, targeted drug delivery is of great interest in the field of medicine. The study of compounds capable of permeating cell membranes is a major problem in this area. The synthesis of pharmacologically active compounds includes the formation of structures with various combinations of pharmacophore fragments and properties. Amphiphilic compounds tend to exhibit membranotropic activity. From this point of view, the modification of natural products, especially terpenoids, is of particular interest. Terpenoid structures are used as membrane anchors in the development of modulators for membrane-integrated proteins or structures for creating nanocontainers. In this paper we synthesized a number of water-soluble amphiphilic meroterpenoids containing a charged pyridinium fragment on the basis of acyclic terpene alcohols. Residue of terpene alcohols – geraniol (monoterpenol), farnesol (sesquiterpenol), and phytol (diterpenol) – were used as the hydrophobic part of the amphiphilic structure. Linear acyclic alcohols are commercially available reagents and have a structure similar to that of polyprenols in archaeal lipids, which made it possible to obtain synthetic lipid-like meroterpenoids capable of self-assembly in aqueous solutions. The charged pyridinium fragment, which is included in numerous natural compounds, was of interest as a polar component. This meroterpenoids are synthetic analogs of archaeal lipids. It was shown that the studied meroterpenoids form nanosized aggregates in aqueous solutions by the method of dynamic light scattering and the Doppler microelectrophoresis method. Turbidimetric titration on model dipalmitoylphosphatidylcholine vesicles revealed that the synthesized compounds are embedded into the bilayer membrane without destroying it. Self-assembled aggregates of synthesized compounds in water can find application for drug delivery – in the creation of nanocontainers containing membrane anchors capable of interacting with the outer surface of the cell (lipid membrane).

A detailed investigation on interactions between magnetite nanoparticles functionalized with aminated chitosan and a cell model membrane.

Magnetite nanoparticles are promising materials for application in magnetic resonance imaging, targeted drug delivery, enzyme immobilization and cancer therapies based on hyperthermia thanks to their biocompatibility, wide chemical affinity and superparamagnetic properties. However, there is still the lack of the knowledge of interactions between magnetite nanoparticles covered with the bioactive polymers and biological cells. In order to fulfil this gap, we have investigated interactions of newly synthetized magnetite nanoparticles functionalized with aminated chitosan (Fe3O4-aminated chitosan) and a model biological membrane made of dipalmitoylphosphatidylcholine (DPPC) using a Langmuir technique. Surface pressure-mean area per DPPC molecule isotherms and Brewster angle microscope images (BAM) recorded during compression of the two-component Fe3O4-aminated chitosan:DPPC films revealed the strong influence of the Fe3O4-aminated chitosan nanoparticles on the stability, phase state and structure of the phospholipid membrane. The studies on the adsorption/incorporation process of the Fe3O4-aminated chitosan nanoparticles showed that they can adsorb/incorporate into the DPPC model membrane at the surface pressure corresponding to this present in the cellular membrane under the biological conditions (35mN·m-1). The number of the adsorbed/incorporated Fe3O4-aminated chitosan nanoparticles can be regulated by the nanoparticles concentration in the neighbourhood of the DPPC model membrane even at high surface pressure of 35mN·m-1.

Probable Transmembrane Amyloid α-Helix Bundles Capable of Conducting Ca2+ Ions.

Amyloid β (Aβ) peptides are considered the major causative agents of Alzheimer's disease (AD). In a widely accepted mechanism for AD pathogenesis, Aβ peptides are proposed to play multiple roles in damaging brain cells and their synaptic communications. Due to the heterogeneous nature of Aβ oligomers, their in vivo structures have not been understood. Most experimental and computational studies favored β-rich structures of Aβ as observed in Aβ fibrils. In this in silico study, we investigated an alternative perspective on the structures and function of Aβ oligomers in the cell membrane. Transmembrane α-helix bundles of the Aβ17-42 tetramer and trimer were observed in extensive temperature replica exchange molecular dynamics (REMD) simulations. We observed three minima on the free-energy landscape of each oligomer, namely, A, B, and C for the tetramer and D, E, and F for the trimer. Except for F, the minima consist of 4 or 3 parallel helices spanning across the membrane model dipalmitoylphosphatidylcholine. Replica exchange molecular dynamics-umbrella sampling (REMD-US) simulation was applied to study the process of a Ca2+ crossing the pore formed by the α-helix bundles in A-E in comparison to that in a calcium channel and a proton channel. REMD-US reveals that A, C, and D allow Ca2+ to cross their pore with a free-energy barrier comparable to that found for the calcium channel. In contrast, the free-energy barrier of a Ca2+ ion crossing B, E, and the proton channel is significantly higher. This result suggests that Aβ peptide oligomers could form transmembrane α-helix bundles that provide feasible pathways for Ca2+ transport. This is an intriguing observation that will stimulate further studies.

Disruption of gel phase lipid packing efficiency by sucralose studied with merocyanine 540

Sucralose, an artificial sweetener, displays very different behavior towards membranes than its synthetic precursor sucrose. The impact of both sugars on model dipalmitoylphosphatidylcholine model membranes was investigated using absorbance and flourescence spectroscopy and the membrane probe merocyanine 540. This probe molecule is highly sensitive to changes in membrane packing, microviscosity and polarity. This work focuses on the impact of sugars on the outer leaflet of unilamellar dipalmitoyl phosphatidylcholine model membranes. The choice of lipid permits access to the gel phase at room temperature and incorporation of the dye after liposome formation allows us to examine the direct impact of the sugar on the outer leaflet while maximizing the response of the dye to changes in the bilayer. The results demonstrate that sucrose has no impact on the packing efficiency of lipids in unilamellar DPPC vesicles in the gel phase. Conversely sucralose decreases the packing efficiency of lipids in the gel phase and results in decreased microviscosity and increased membrane fluidity, which may be as a result of water disruption at the membrane water interface.

The Localization of Phenolic Compounds in Liposomal Bilayers and Their Effects on Surface Characteristics and Colloidal Stability.

The interactions with and effects of five chemically distinct, bioactive phenolic compounds on the lipid bilayers of model dipalmitoylphosphatidylcholine (DPPC) liposomes were investigated. Complementary analytical techniques, including differential scanning calorimetry (DSC) and phosphorus and proton nuclear magnetic resonance spectroscopy (NMR), were employed in order to determine the location of the compounds within the bilayer and to correlate location with their effects on bilayer characteristics and liposomal stability. As compared to the phenolic compounds localized in the glycerol region of the DPPC head group within the bilayer, which enhanced the colloidal stability of the liposomes, compounds located closer to the center of the bilayer reduced vesicle stability as a function of time. Molecules present in the upper region of liposomal DPPC acyl chains (C1-C10) inhibited liposomal aggregation and size increase, perhaps due to tighter packing of adjoining DPPC molecules and increased surface exposure of DPPC phosphate head groups. These data may be useful for designing liposomal systems containing hydrophobic phenols and other small molecules, selecting appropriate analytical methods for determining their location within liposomal bilayers, and predicting their effects on liposome characteristics early in the liposome formulation development process.

Adsorption behavior of magnetite nanoparticles into the DPPC model membranes

In this report, we have studied the adsorption behavior of Fe3O4 nanoparticles into dipalmitoylphosphatidylcholine (DPPC) monolayer. Adsorption kinetics (π–t) process as well as the surface pressure (π–A) isotherms were monitored by Langmuir Wilhelmy plate. The measurement data indicated the Fe3O4 nanoparticles incorporated into the monolayer at the air–water interface. The lifting area/molecule isotherms of DPPC monolayers increased with the increasing concentration of Fe3O4 in the subphase, however, the values of elasticity reduced. The curves of π–t were well fitted by single exponential association equation. Observation by atomic force microscopy (AFM) on monolayers extracted at 5mN/m and 15mN/m suggested that the different interaction of Fe3O4 with DPPC monolayer depended on surface pressure of monolayers and concentration in the subphase. The results of observations were in agreement with the fitted results.

A 2H magic-angle spinning solid-state NMR characterisation of lipid membranes in intact bacteria

This work proposes a new approach to characterize cell membranes in intact cells by 2H solid-state nuclear magnetic resonance (NMR) in only a few hours using magic-angle spinning (MAS) and spectral moment analysis. The method was first validated on model dipalmitoylphosphatidylcholine (DPPC) membranes, allowing the detection of lipid fluctuations below the main transition temperature. Then the lipid dynamics in Escherichia coli membranes was compared in bacteria grown under different diets. More specifically, deuterated palmitic acid was used to isotopically label the phospholipid acyl chains in bacteria membranes, with or without the presence of protonated oleic acid. Our results showed improved lipid fluidity when bacteria were grown in the presence of oleic acid, which helps preserving the natural fatty acid profile in E. coli membranes. The MAS 2H solid-state NMR study of membranes combined with spectral moment analysis showed to be a fast method compatible with in vivo bacterial studies, and should also be applicable to other micro-organisms to obtain molecular information on living cells by solid-state NMR.

A comparative study of the effects of cholesterol and desmosterol on zwitterionic DPPC model membranes

Desmosterol is a direct biosynthetic precursor of cholesterol in Bloch biochemical pathway of cholesterol biosynthesis and differs with cholesterol only by a double bond in carbon 24. In this study, we aimed to research for the first time comparative effects of cholesterol and its precursor desmosterol on dipalmitoyl phosphatidylcholine (DPPC) multilamellar vesicles (MLVs) by utilizing Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). Our DSC studies reveal that with the addition of increasing desmosterol and cholesterol concentrations into pure DPPC MLVs, the pretransition disappears, the main phase transition shifts to lower temperatures and then disappears. While the main phase transition is abolished at 25mol% concentration of desmosterol, this disappearance of the main phase transition occurs at cholesterol concentration above 30mol%. Our FTIR studies show that both desmosterol and cholesterol decrease the order in the gel phase, whereas they increase it in the liquid crystalline phase. Importantly, we found that the effect of desmosterol on membrane order is weaker than that of cholesterol in both phases. Moreover, desmosterol and cholesterol increase the dynamics of DPPC membranes in the gel phase, while they decrease it in the liquid crystalline phase. Both sterols also induce a decrease in the wavenumber values of the CO stretching and PO2− antisymmetric double stretching bands of DPPC both in the gel and liquid crystalline phases, which points out hydrogen bonding in between the hydroxyl group of both sterols and the carbonyl and phosphate groups of DPPC membranes.

Agomelatine strongly interacts with zwitterionic DPPC and charged DPPG membranes

Depression is one of the most common psychiatric diseases in the population. Agomelatine is a novel antidepressant drug with melatonin receptor agonistic and serotonin 5-HT2C antagonistic properties. Furthermore, being a melatonergic drug, agomelatine has the potential of being used in therapeutic applications like melatonin as an antioxidant, anti-inflammatory and antiapoptotic drug. The action mechanism of agomelatine on the membrane structure has not been clarified yet. In the present study, we aimed to investigate the interaction of agomelatine with model membranes of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylgylcerol (DPPG) by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). We found that agomelatine interacts with the head group in such a manner that it destabilizes the membrane architecture to a large extent. Thus, agomelatine causes alterations in the order, packing and dynamics of the DPPC and DPPG model membranes. Our results suggest that agomelatine strongly interacts with zwitterionic and charged membrane phospholipids. Because lipid structure and dynamics may have influence on the structure of membrane bound proteins and affect the signal transduction systems of membranes, these effects of agomelatine may be important in its action mechanism.

Refined OPLS all-atom force field for saturated phosphatidylcholine bilayers at full hydration.

We report parametrization of dipalmitoyl-phosphatidylcholine (DPPC) in the framework of the Optimized Parameters for Liquid Simulations all-atom (OPLS-AA) force field. We chose DPPC as it is one of the most studied phospholipid species and thus has plenty of experimental data necessary for model validation, and it is also one of the highly important and abundant lipid types, e.g., in lung surfactant. Overall, PCs have not been previously parametrized in the OPLS-AA force field; thus, there is a need to derive its bonding and nonbonding parameters for both the polar and nonpolar parts of the molecule. In the present study, we determined the parameters for torsion angles in the phosphatidylcholine and glycerol moieties and in the acyl chains, as well the partial atomic charges. In these calculations, we used three methods: (1) Hartree-Fock (HF), (2) second order Møller-Plesset perturbation theory (MP2), and (3) density functional theory (DFT). We also tested the effect of the polar environment by using the polarizable continuum model (PCM), and for acyl chains the van der Waals parameters were also adjusted. In effect, six parameter sets were generated and tested on a DPPC bilayer. Out of these six sets, only one was found to be able to satisfactorily reproduce experimental data for the lipid bilayer. The successful DPPC model was obtained from MP2 calculations in an implicit polar environment (PCM).

Probing of the combined effect of bisquaternary ammonium antimicrobial agents and acetylsalicylic acid on model phospholipid membranes: differential scanning calorimetry and mass spectrometry studies

A model molecular biosystem of hydrated dipalmitoylphosphatidylcholine (DPPC) bilayers that mimics cell biomembranes is used to probe combined membranotropic effects of drugs by instrumental techniques of molecular biophysics. Differential scanning calorimetry reveals that doping of the DPPC model membrane with individual bisquaternary ammonium compounds (BQAC) decamethoxinum, ethonium, thionium and acetylsalicylic acid (ASA) leads to lowering of the membrane melting temperature (Tm) pointing to membrane fluidization. Combined application of the basic BQAC and acidic ASA causes an opposite effect on Tm (increase), corresponding to the membrane densification. Thus, modulation of the membranotropic effects upon combined use of the drugs studied can be revealed at the level of model membranes. Formation of noncovalent supramolecular complexes of the individual BQACs and ASA with DPPC molecules, which may be involved in the mechanism of the drug-membrane interaction at the molecular level, is demonstrated by electrospray ionization (ESI) mass spectrometry. In the ternary (DPPC + ASA + BQAC) model systems, the stable complexes of the BQAC dication with the ASA anion, which may be responsible for modulation of the membranotropic effects of the drugs, were recorded by ESI mass spectrometry. The proposed approach can be further developed for preliminary evaluation of the combined effects of the drugs at the level of model lipid membranes prior to tests on living organisms.

P.2.b.039 An observational study to evaluate social and occupational functioning in depressed patients treated with escitalopram

Depression is one of the most common psychiatric diseases in the population. Agomelatine is a novel antidepressant drug with melatonin receptor agonistic and serotonin 5-HT2C antagonistic properties. Furthermore, being a melatonergic drug, agomelatine has the potential of being used in therapeutic applications like melatonin as an antioxidant, anti-inflammatory and antiapoptotic drug. The action mechanism of agomelatine on the membrane structure has not been clarified yet. In the present study, we aimed to investigate the interaction of agomelatine with model membranes of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylgylcerol (DPPG) by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). We found that agomelatine interacts with the head group in such a manner that it destabilizes the membrane architecture to a large extent. Thus, agomelatine causes alterations in the order, packing and dynamics of the DPPC and DPPG model membranes. Our results suggest that agomelatine strongly interacts with zwitterionic and charged membrane phospholipids. Because lipid structure and dynamics may have influence on the structure of membrane bound proteins and affect the signal transduction systems of membranes, these effects of agomelatine may be important in its action mechanism.

Мембранотропные свойства урокановой кислоты

The effects of urocanic acid (UA) on thermodynamic parameters of model dipalmitoylphosphatidylcholine (DPPC) lipid membrane have been studied by means of differential scanning calorimetry (DSC). The observed ordering effect of UA on the lipid bilayer is reflected in the increase in both the main phase transition temperature and cooperative unit size of the lipid membrane. Analysis of FTIR spectra suggests localization of UA molecules in the vicinity of the polar heads and carbonyl groups of DPPC due to electrostatic interactions and H-bonds. On the basis of experimental data obtained and geometry parameters of UA and DPPC molecules, some variants of the UA localization in DPPC bilayer were discussed.

Influence of fluphenazine dihydrochloride on model dipalmitoylphosphatidylcholine membranes and human genotoxically damaged lymphocyte cultures

The membrane interactions can play a vital role in chemosensitizing activity of fluphenazine dihydrochloride, an inhibitor of P-glycoprotein transport function. In in vitro testings of the influence of fluphenazine dihydrochloride on model dipalmitoylphosphatidylcholine membranes and on human lymphocyte cultures, genotoxically damaged by benzo[a]pyrene, differential scanning calorimetry and rhodamine 123 retention test were applied. The results of both testings shown that the membrane interactions of fluphenazine dihydrochloride in model membrane structure and the chemosensitizing effect of this compound in examined human lymphocyte cultures, depend on its concentration in a sample.