Dipalmitoylphosphatidylglycerol Research Articles

Dendrimeric HIV-peptide delivery nanosystem affects lipid membranes structure

The aim of this study was to evaluate the nature and mechanisms of interaction between HIV peptide/dendrimer complexes (dendriplex) and artificial lipid membranes, such as large unilayered vesicles (LUV) and lipid monolayers in the air–water interface. Dendriplexes were combined as one of three HIV-derived peptides (Gp160, P24 and Nef) and one of two cationic phosphorus dendrimers (CPD-G3 and CPD-G4). LUVs were formed of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) or of a mixture of DMPC and dipalmitoyl-phosphatidylglycerol (DPPG). Interactions between dendriplexes and vesicles were characterized by dynamic light scattering (DLS), fluorescence anisotropy, differential scanning calorimetry (DSC) and Langmuir–Blodgett methods. The morphology of formed systems was examined by transmission electron microscopy (TEM). The results suggest that dendriplexes interact with both hydrophobic and hydrophilic regions of lipid bilayers. The interactions between dendriplexes and negatively charged lipids (DMPC–DPPG) were stronger than those between dendriplexes and liposomes composed of zwitterionic lipids (DMPC). The former were primarily of electrostatic nature due to the positive charge of dendriplexes and the negative charge of the membrane, whereas the latter can be attributed to disturbances in the hydrophobic domain of the membrane. Obtained results provide new information about mechanisms of interaction between lipid membranes and nanocomplexes formed with HIV-derived peptides and phosphorus dendrimers. These data could be important for the choosing the appropriate antigen delivery vehicle in the new vaccines against HIV infection.

Interactions of l-arginine with Langmuir monolayers of common phospholipids at the air-water interface

The interactions of l-arginine (l-arg) with Langmuir monolayers of three most common phospholipids, which are sodium salt of dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine (DPPE), have been investigated at the air-water interface. The surface pressure-area (π-A) isotherms of these monolayers have been measured with a film balance and monolayer morphology has been observed by a Brewster angle microscopy (BAM). The DPPG monolayers on pure water do not show any phase transition but show irregular shaped condensed phases formed just after evaporation of the solvent at 20 °C. However, this monolayer on l-arg solution subphase indicates a first-order phase transition from liquid expanded to liquid condensed (LE-LC) phases and forms LC domains at the same temperature. With an increase in the l-arg concentration in the subphase up to 5.0 × 10−4 M, the π-A shows an overall increasingly greater expansion in the molecular area. All of the π-A isotherms recorded on ≥5.0 × 10−4 M l-arg solution subphases almost coincide with each other. These changes in the phase behavior have been explained by the fact that l-arg having guanidinium cationic group undergoes strong hydrogen bonding interaction with the anionic phosphatidylglycerol (PG-) head group. The bonding between two molecules is further strengthened by electrostatic attraction between cationic l-arg and anionic PG- ions. The BAM observation of the monolayer morphology supports this explanation. On the other hand, a very negligible interaction has been observed between l-arg and DPPC or DPPE monolayers. The π-A isotherms in the presence of l-arg for both the amphiphiles show a very little expansion only in the LE phase region, but coincide in the so called solid phase region. The monolayer morphology of both the monolayers also supports these results. This little effect of expansion in the LE region may be explained by the ion-pair formation between cationic l-arg and anionic head groups in the monolayers at lower pressures. However, due to compression at high pressure, the l-arg molecules are squeezed out from the amphiphile head groups.

Evaluation of the effects in cellular membrane models of antitrypanosomal poly-thymolformaldehyde (PTF) using Langmuir monolayers

The polymerization of bioactive compounds may be interesting because the supramolecular structures formed can boost biological action on microorganism membranes. In the present work, poly-thymolformaldehyde (PTF) activity, prepared by condensation of thymol and formaldehyde, was evaluated against trypomastigote forms of Trypanosoma cruzi and related with the physicochemical changes provided by the incorporation of the compound in protozoan cell membrane models. PTF exhibited an EC50 value of 23.4 μg/mL and no toxicity against mammalian cells (CC50 > 200 μg/mL). To understand the molecular action of PTF as an antiprotozoal candidate, this compound was incorporated in Langmuir monolayers of dipalmitoylphosphatidylglycerol (DPPG) as a model for parasite cell membranes. PTF shifted DPPG surface pressure-area isotherms to higher areas, indicating its incorporation in the lipid films. Additionally, it changed the thermodynamic, compressional, structural, and morphological properties of the floating monolayers, decreasing the collapse pressure, reducing the surface elasticity, and segregating molecules at the interface, forming domains with different reflectivities. Infrared spectroscopy showed that the lipid films with PTF presented an increased rate of gauche/all-trans conformers for the methylene groups from the acyl chains, indicating molecular disorder. Therefore, these results show that PTF alters the physicochemical properties of DPPG monolayers as a model for protozoa cell membranes, which can enhance the comprehension of the parasitic action of PTF against T. cruzi.

Advanced spray dried proliposomes of amphotericin B lung surfactant-mimic phospholipid microparticles/nanoparticles as dry powder inhalers for targeted pulmonary drug delivery

The purpose of this study was to design, develop and characterize inhalable proliposomal microparticles/nanoparticles of Amphotericin B (AmB) with synthetic phospholipids, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) which are lung surfactant-mimic phospholipids. Organic solutions of AmB and phospholipids, were co-spray dried using an advanced closed-mode system and a high performance cyclone. Scanning electron microscopy (SEM) was employed to visualize the surface structure, morphology, and particles size. The residual water content of the proliposomes was quantified by Karl Fisher coulometric titration (KFT). Degree of crystallinity/non-crystallinity was measured by X-ray powder diffraction (XRPD). Phase behavior was measured by differential scanning calorimetry. The chemical composition by molecular fingerprinting was established using attenuated total reflectance (ATR)-Fourier-transform infrared (FTIR) spectroscopy. The amount of AmB loaded into the proliposomes was quantified using UV-VIS spectroscopy. The in vitro aerosol dispersion performance was conducted using the Next Generation Impactor (NGI) and the human dry powder inhaler (DPI) (Handihaler®) that is FDA-approved. Different human lung cell lines were employed to demonstrate in vitro safety as a function of dose and formulation. Smooth, spherical microparticles/nanoparticles were formed at medium and high spray drying pump rates and had low residual water content. A characteristic peak in the XRPD diffraction pattern as well as an endotherm in DSC confirmed the presence of the lipid bilayer structure characteristic in the DPPC/DPPG proliposomal systems. Superior in vitro aerosol performance was achieved with engineered microparticles/nanoparticles demonstrating suitability for targeted pulmonary drug delivery as inhalable dry powders. The in vitro cellular studies demonstrated that the formulated proliposomes are safe. These AmB proliposomes can be a better option for targeted treatment of severe pulmonary fungal infections.

X-Ray Reflectivity and Diffraction Studies of Doxorubicin Binding to Model Lipid Membranes

The effect of anticancer antibiotic doxorubicin on structural organization of anionic lipid monolayers has been studied. X-ray reflectivity and grazing incidence diffraction techniques were applied to monitor the changes in 2D structure and electron density distribution of Langmuir monolayer composed of negatively charged dipalmitoylphosphatidylglycerol (DPPG) and dioleoylphosphatidylserine (DOPS). For comparison, monolayer of zwitterionic dipalmitoylphosphatidylethanolamine (DPPE) also was investigated. The presented experimental results suggest that doxorubicin interaction with anionic lipid monolayers (DPPG and DOPS) proceeds preferentially via electrostatic attraction—positively charged amino groups of doxorubicin bind to negatively charged head groups of phospholipid molecules. Based on the obtained data, the penetration of doxorubicin into the hydrophobic part of anionic lipid monolayers does not occur. X-ray measurements on DPPE monolayer indicated that doxorubicin did not cause any significant alterations of molecular packing in condensed monolayer of zwitterionic DPPE molecules.

Investigating the interactions of corona-free SWCNTs and cell membrane models using sum-frequency generation.

The understanding of the interactions between biomolecules and nanomaterials is of great importance in many areas of nanomedicine and bioapplications. Numerous studies in this area have been performed. However, toxicological aspects involving the interaction between phospholipids and carbon nanotubes (CNTs) remain undefined, especially for those cases in which a protein corona is not formed around the nanomaterial (corona-free nanomaterials). This study focuses on the interaction of Langmuir films of dipalmitoylphosphatidylglycerol (DPPG) and dipalmitoylphosphatidylcholine (DPPC) with corona-free, single-walled CNTs. Surface pressure-area isotherms and sum-frequency generation (SFG) vibrational spectroscopy, a non-linear optical technique used to study surfaces and interfaces, were used to investigate the lipid tail orientation and conformation, aiming to understand the interactions between phospholipids and single walled carbon nanotubes functionalized by carboxylic acid (SWCNTs-COOH) at the air-water interface under low ionic strength conditions. Data from isotherms and SFG spectra revealed that the SWCNT adsorption at the air-water interface is induced by the presence of both lipids, although at a lesser extent for DPPG due to its anionic head group, which could result in repulsion of SWCNTs-COOH that also bear a negative charge. Furthermore, lipid monolayers remained conformationally ordered, indicating insertion of SWCNTs into the lipid monolayer. Our results corroborate previous works and simulations in the literature, but made it possible to perform an in-depth investigation of the interaction of these nanomaterials with components of phospholipid membranes.

Simultaneous Quantification of DPPG, DEPC and Cholesterol in Propofol Liposome by HPLC-ELSD Using Alkaline Hydrolysis.

A high-performance liquid chromatography method with evaporative light-scattering detection (ELSD) was performed for simultaneous determination of dipalmitoyl phosphatidylglycerol (DPPG), dierucoyl phosphatidylcholine (DEPC) and cholesterol in propofol liposome by the pretreatment of alkaline hydrolysis (temperature, concentration of KOH anhydrous ethanol solution and reaction time were 90°C, 1mol · L-1 and 10min, respectively). The analysis was carried out on an Agilent TC-C18 column (4.6mm×250mm, 5μm) with isocratic elution of methanol and 0.1% acetic acid aqueous solution (95:5, v/v) at a flow rate of 1.0mL· min-1. The column temperature was 30°C. The drift tube temperature of the ELSD system was set at 30°C, and the pressure of carrier gas was 350KPa. The regression equation revealed a good linear relationship (r=0.9990-0.9993) during the test ranges. The RSD of stability and repeatability (n=6) was found to be less than 1.96 and 1.46%, respectively. The average recoveries ranged from 97.90 to 101.00%. The proposed method was validated and showed good precision, stability, repeatability and recovery, which indicated that the method could be readily utilized as a quality evaluation method for the determination of DPPG, DEPC and cholesterol in propofol liposome.

Enhanced chain packing achieved via putative headgroup ion-triplet formation in binary anionic lipid/cationic surfactant mixed monolayers

Lipid/surfactant miscibility was investigated in monolayers composed of binary mixtures of dipalmitoylphosphatidylglycerol (DPPG) and dihexadecyldimethylammonium bromide (DHDAB). Langmuir monolayers formed from biomimetic DPPG/DHDAB mixtures based on the anionic:cationic lipid ratios observed in the bacterium Staphylococcus aureus (7:3 and 1:1) were examined alongside those of the pure amphiphiles and a surfactant rich 3:7 mixture. Using a combination of GIXD, TRXF and IRRAS, DPPG/DHDAB 1:1 monolayers were found to form a more stabilised condensed phase compared to pure DPPG, which was composed entirely of electrostatically neutral ion pairs, analogous to the so-called catanionic amphiphiles spontaneously formed by single-chain surfactants with opposing headgroup charges. Despite the lack of lateral charge repulsion the ion paired phase of DPPG/DHDAB exhibited slightly looser chain packing that was observed for DPPG indicating a significant steric effect on packing geometry caused by ion pair formation. Surprisingly, the 7:3 mixture of DPPG/DHDAB formed a completely condensed phase, with no isotherm transitions, in which the chain packing was significantly closer than was found for either DPPG or the totally ion paired monolayer. It is postulated that this mixture forms a distinct DPPG/DHDAB/DPPG ion triplet phase in which the overall negative charge is delocalised across the headgroups. Vesicles composed from the 7:3 mixture formed highly stable dispersions with an increased gel to liquid crystalline phase transition temperature with respect to its pure components. Increasing the proportion of DHDAB above 50 mol% led to demixing between the condensed ion paired phase and the more fluid surfactant, as was clearly observed in epifluorescence images taken of the surface films.

PREPARATION AND CHARACTERIZATION OF LIPOSOMAL DELIVERY SYSTEM OF NATURAL HEME PROTEIN

Objective: The objective of the present study was to develop and optimize the methods for preparation and characterization of the liposomal delivery system of natural heme protein.
 Methods: Cytochrome C containing liposomes (Cyt-LS) were prepared by high-pressure homogenization technique using phosphatidylcholine (PC) and dipalmitoyl phosphatidylglycerol (DPPG). Nanoparticles were characterized by using: dynamic light scattering, zeta potential measurements, scanning electron microscopy and HPLC. The specific activity was studied in vitro.
 Results: The study of homogenization regimes for obtaining unilamellar Cyt-LS was carried out. The selected temperature regime of homogenization was kept within 38–44 °С with optimal homogenization pressure of 800 bar. The obtained Cyt-LS were characterized by the main physicochemical parameters showed: Encapsulation efficiency 95.8±2.0%, Zeta potential-57±1.0 mV, pH-6.95±0.05. Phospholipid impurities had the following content: lysophosphatidylcholine-0.60±0.05% and free fatty acids-0.4±0.05%. The average particle diameter was 156±2 nm. Also, the size of Cyt-LS particles was confirmed by the ability of emulsion subjected to the sterilizing filtration with the preservation of its main physicochemical properties. Cyt-LS exhibit specific activity, similar to non-liposomal Cyt-C solution.
 Conclusion: The formulation of the liposomal delivery system of heme protein was successfully prepared using natural components and evaluated for different parameters.

The effects of radioprotectant and potential antioxidant agent amifostine on the structure and dynamics of DPPC and DPPG liposomes

Agents capable of scavenging ROS have attracted attention recently because of their potential use as antioxidative agents. Amifostine, a ROS scavenger, has the potential to be used as an antioxidant in therapeutic applications. In this study, the effect of amifostine on neutral zwitterionic dipalmitoylphosphatidylcholine (DPPC) and anionic dipalmitoylphosphatidylglycerol (DPPG) model membranes' structure and dynamics is aimed to be examined by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). Our results revealed that amifostine at concentrations used (1–24 mol%) does not induce any important alteration in the shape of phase transition curve and phase transition temperature in the DPPC and DPPG membranes. High concentrations of amifostine slightly increased the acyl chain flexibility of DPPC membranes in the liquid crystalline phase and DPPG membranes in the gel phase. A lessening in the dynamics of DPPC liposomes was observed for all concentrations of amifostine in both phases but slight dual effect was observed only in the gel phase as a decrease in dynamics at low concentrations and an increase at higher concentrations of amifostine in DPPG liposomes. Additionally, strong hydrogen bonding was observed for both CO and PO2− groups in case of DPPC and for PO2− groups in case of DPPG. Dehydration around the CO regions occurred in case of DPPG. Accordingly, amifostine is proposed to be interacting strongly with zwitterionic and negatively charged membrane head groups and glycerol backbone in all concentrations and because of this interaction it causes some changes in lipid order and dynamics especially at high concentrations.

Salt effect on bilayer phase transitions of dipalmitoylphosphatidylglycerol in saline water under high pressure

ABSTRACTThe phase transitions of dipalmitoylphosphatidylglycerol (DPPG) bilayer membrane at high NaCl concentrations under high pressure were investigated to construct the temperature–pressure phase diagram and to determine phase-transition properties. The constructed phase diagrams exhibited qualitative resemblance to that of the dipalmitoylphosphatidylcholine (DPPC) bilayer membrane: they showed the gel-phase polymorphism including the pressure-induced bilayer interdigitation. The phase-transition properties of the DPPG bilayer membrane changed in a salt concentration-dependent manner. We discussed the salt effect on the DPPG bilayer membrane from the variation in interactions between the polar head groups of the PG molecules.

Liposome-Based Biosensors Using Phytase Immobilized on Polypyrrole Films for Phytic Acid Determination

Abstract Phytase was immobilized onto electrochemically prepared polypyrrole (PPy) films either in the free, native form (Phy) or encapsulated in phospholipid dipalmitoyl phosphatidylglycerol (DPPG) liposomes (lipo-Phy). The incorporation of Phy into the PPy matrix was verified using cyclic voltammetry, polarization-modulated infrared reflection absorption spectroscopy, and scanning electron microscopy. PPy, PPy/Phy and PPy/lipo-Phy films were characterized by amperometric experiments in phytic acid (PA) solutions at different concentrations. PPy/lipo-Phy showed a more sensitive response, which was confirmed in stable current vs concentration and current vs time curves, and by a superior analytical performance with a saturation concentration of 3.0 mmol L−1 PA. A multidimensional projection technique, IDMAP, was used to project the voltammetric data, and confirmed the higher selectivity for PPy/lipo-Phy by distinguishing PA in a specific range of concentrations.

Interaction of the cholesterol reducing agent simvastatin with zwitterionic DPPC and charged DPPG phospholipid membranes

Simvastatin is a lipid-lowering drug in the pharmaceutical group statins. Interaction of a drug with lipids may define its role in the system and be critical for its pharmacological activity. We examined the interactions of simvastatin with zwitterionic dipalmitoyl phosphatidylcholine (DPPC) and anionic dipalmitoyl phosphatidylglycerol (DPPG) multilamellar vesicles (MLVs) as a function of temperature at different simvastatin concentrations using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The FTIR results indicate that the effect of simvastatin on membrane structure and dynamics depends on the type of membrane lipids. In anionic DPPG MLVs, high simvastatin concentrations (12, 18, 24 mol%) change the position of the CH2 antisymmetric stretching mode to lower wavenumber values, implying an ordering effect. However, in zwitterionic DPPC MLVs, high concentrations of simvastatin disorder systems both in the gel and liquid crystalline phases. Moreover, in DPPG and DPPC MLVs, simvastatin has opposite dual effects on membrane dynamics. The bandwidth of the CH2 antisymmetric stretching modes increases in DPPG MLVs, implying an increase in the dynamics, whereas it decreases in DPPC MLVs. Simvastatin caused broadening of the phase transition peaks and formation of shoulders on the phase transition peaks in DSC curves, indicating multi-domain formations in the phospholipid membranes. Because physical features of membranes such as lipid order and fluidity may be changed with the bioactivity of drugs, opposing effects of simvastatin on the order and dynamics of neutral and charged phospholipids may be critical to deduce the action mechanism of the drug and estimate drug-membrane interactions.

Interaction of Short Pentavalent Cationic Peptides with Negatively Charged DPPG Monolayers and Bilayers: Influence of Peptide Modifications on Binding.

The binding of oligopeptides with the structure (RX)4R and (KXX)4K, with X being the amino acid G or A, to lipid monolayers and bilayers of dipalmitoyl-phosphatidylglycerol (DPPG) was studied and compared to the binding effects of peptides with the structure (KX)4K. The monolayer adsorption experiments again showed the superposition of condensation effects due to charge compensation and insertion of amino acid side chains leading to expansion of the monolayer. The latter effect was enhanced when glycine was replaced by alanine. The thermotropic phase behavior of dipalmitoyl-phosphatidylglycerol (DPPG) bilayer membranes and their mixtures with short cationic model peptides was investigated by differential scanning calorimetry and infrared spectroscopy. Increasing the charge distance of the lysine residues in the series (K)5, (KG)4K, and (KGG)4K results in an upshift of the main phase transition of DPPG up to 5 K, as predicted for pure electrostatic binding. All peptides exhibit only unordered structures in bulk solution as well as when bound to DPPG bilayers. (KGG)4K additionally shows a high propensity of turn structures due to its flexibility. The exchange of glycine by alanine in (KAA)4K leads only to a marginal increase in Tm, in contrast to the binding of (KA)4K where the formation of intervesicular antiparallel β-sheets occurs, leading to a much more pronounced stabilization of the gel phase. This shows that the sequence and flexibility of the oligopeptides has an important influence on the formation of secondary structures bound to the bilayers. Binding of (RX)4R peptides to DPPG bilayers has almost no influence on the lipid phase transition in bilayers. Here, condensation and insertion effects almost compensate, as the results of monolayer experiments show. This is due to the higher propensity of arginine side chains to insert into the lipid headgroup region.

Thermodynamic Characterization of Mixed Monolayers of a Novel Oxazolidine Derivative and Phospholipids.

Oxazolidine derivatives (OxD) are five ring-membered compounds that contain at least one oxygen and nitrogen in their molecular structure. OxD are known due to several therapeutic activities such as anticancer and antibiotic properties. In this paper, we performed a thermodynamic analysis of the mixed films composed by dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphoethanolamine (DPPE), dipalmitoyl phosphatidylcholine (DPPC) or L-α phosphatidylcholine (PC) with a novel oxazolidine derivate (OxD). Relevant thermodynamic parameters such as excess areas (ΔAE), excess free energies (ΔG), and Gibbs free energy of mixing (AGmix) were derived from the surface pressure data. The topographical analysis was performed using atomic force microscopy. Based on the calculated values of the thermodynamic parameters, we observed that the miscibility of the mixed films was directly dependent on their composition. DPPG/OxD and DPPE/OxD systems present the best-mixed character at low pressures at OxD molar fraction equivalent to 0.25.

A combined FTIR and DSC study on the bilayer-stabilising effect of electrostatic interactions in ion paired lipids

Investigating lipid ion pair formation is important for understanding the mechanisms of lipid-mediated drug resistance in bacteria. In this study we have used the charged amphiphiles dipalmitoylphosphatidylglycerol (DPPG) and dihexadecyldimethylammonium bromide (DHDAB), as a model to evaluate the formation of ion pairs by a combined Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analysis. FTIR was employed to study the environment of the DPPC headgroup phosphate and lipid/surfactant alkane chains, in vesicles formed by the two amphiphiles mixed in various molar ratios. An increase of the absorbance ratio of 1221-1201 cm-1 in the asymmetric phosphate stretching mode was found to follow a sigmoidal relationship with the proportion of DHDAB, increasing to a plateau above a DPPG/DHDAB 1:1 molar ratio of, providing evidence that the PG headgroup phosphate is involved in ion pairing. A consistent red shift was measured for the position of the symmetric CH2 stretch band for the lipid/surfactant 1:1 molar ratio mixture, which is indicative of an increased ordering of the hydrophobic chains. The DSC experiments yielded information about the thermotropic and the mixing behaviour of the lipid/surfactant systems. DPPG and DHDAB seem to form an ion pair with cluster compound characteristics at the equimolar ratio. Most interestingly, the DPPG/DHDAB 2:1 molar ratio mixture is characterized by strong intermolecular interactions, which result in a pronounced stabilization of the gel phase, possibly through the formation of a closely-associated ion triplet configuration in which the charges are delocalised across the headgroups.

An Investigation into the Antibacterial Properties of Citrus and Plant Essential Oils

Langmuir Monolayers of dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG), and E.coli lipid extract were used to investigate the antibacterial properties of essential oils, in particular sweet orange oil. DPPC served as the control membrane while DPPG served as the gram positive bacteria model and E.coli lipid extract was the gram negative bacteria model. The Langmuir Monolayer technique is useful for forming model cell membranes and allows for the analysis of the interactions between phospholipids and their molecular organization in the presence of another molecule. The main chemical in sweet orange oil, limonene, was found to disrupt phospholipid‐phospholipid interactions in all models except for DPPG simply because PG headgroups hydrogen bond with each other and there is no space for the hydrophobic limonene molecule. The largest disruption was observed for the E.coli extract lipids due to the unsaturated tails in these lipids resulting in less tight packing. Monolayers were seen in all three membrane systems to be destabilized as evidenced by the decrease in collapse pressure of the monolayer film but the E.coli lipid extract monolayer was the most affected in terms of fluidity as seen by the compression modulus. The antibacterial effects of orange oil on these systems is currently being compared to that of peppermint oil.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

NIR studies of cholesterol-dependent structural modification of the model lipid bilayer doped with inhalation anesthetics

The influence of cholesterol on the structure of the model lipid bilayers treated with inhalation anesthetics (enflurane, isoflurane, sevoflurane and halothane) was investigated employing near-infrared (NIR) spectroscopy combined with the Principal Component Analysis (PCA). The conformational changes occurring in the hydrophobic area of the lipid bilayers were analyzed using the first overtones of symmetric (2νs) and antisymmetric (2νas) stretching vibrations of the CH2 groups of lipid aliphatic chains. The temperature values of chain-melting phase transition (Tm) of anesthetic-mixed dipalmitoylphosphatidylcholine (DPPC)/cholesterol and dipalmitoylphosphatidylglycerol (DPPG)/cholesterol membranes, which were obtained from the PCA analysis, were compared with cholesterol-free DPPC and DPPG bilayers mixed with inhalation anesthetics.

Atomistic-level study of the interactions between hIAPP protofibrils and membranes: Influence of pH and lipid composition

The pathology of type 2 diabetes mellitus is associated with the aggregation of human islet amyloid polypeptide (hIAPP) and aggregation-mediated membrane disruption. The interactions of hIAPP aggregates with lipid membrane, as well as the effects of pH and lipid composition at the atomic level, remain elusive. Herein, using molecular dynamics simulations, we investigate the interactions of hIAPP protofibrillar oligomers with lipids, and the membrane perturbation that they induce, when they are partially inserted in an anionic dipalmitoyl-phosphatidylglycerol (DPPG) membrane or a mixed dipalmitoyl-phosphatidylcholine (DPPC)/DPPG (7:3) lipid bilayer under acidic/neutral pH conditions. We observed that the tilt angles and insertion depths of the hIAPP protofibril are strongly correlated with the pH and lipid composition. At neutral pH, the tilt angle and insertion depth of hIAPP protofibrils at a DPPG bilayer reach ~52° and ~1.62 nm with respect to the membrane surface, while they become ~77° and ~1.75 nm at a mixed DPPC/DPPG membrane. The calculated tilt angle of hIAPP at DPPG membrane is consistent with a recent chiral sum frequency generation spectroscopic study. The acidic pH induces a smaller tilt angle of ~40° and a shallower insertion depth (~1.24 nm) of hIAPP at the DPPG membrane surface, mainly due to protonation of His18 near the turn region. These differences mainly result from a combination of distinct electrostatic, van der Waals, hydrogen bonding and salt-bridge interactions between hIAPP and lipid bilayers. The hIAPP-membrane interaction energy analysis reveals that besides charged residues K1, R11 and H18, aromatic residues Phe15 and Phe23 also exhibit strong interactions with lipid bilayers, revealing the crucial role of aromatic residues in stabilizing the membrane-bound hIAPP protofibrils. hIAPP-membrane interactions disturb the lipid ordering and the local bilayer thickness around the peptides. Our results provide atomic-level information of membrane interaction of hIAPP protofibrils, revealing pH-dependent and membrane-modulated hIAPP aggregation at the early stage.

The effect of chitin nanoparticles on surface behavior of DPPC/DPPG Langmuir monolayers

The effect of chitin nanoparticles on surface behavior of lipid systems containing dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) is studied by surface pressure (π)-area (A) isotherms, polarization-modulation infrared reflection absorption spectroscopy (PM-IRRAS), Brewster angle microscopy (BAM). The variation of surface behavior of DPPC/DPPG monolayers is induced mainly by electrostatic interactions between nanoparticles and head groups of phospholipids. At lower surface pressure, nanoparticles can penetrate into the monolayers and the positive charges carried by nanoparticles benefits the enrichment of phospholipid molecules at surface, which not only increases the mean molecular area but also hinders the formation of phospholipid liquid-condensed (LC) phase. However, when surface pressure is higher, the nanoparticles flee away from the surface and some of the phospholipid molecules are pulled out of the monolayers together to the subphase and decrease the order degree of the monolayers. Moreover, nanoparticles can destroy the hydrogen-bond between water molecules and phosphate head groups and thus lead to the dehydration of phosphate groups. This work confirms that chitin nanoparticles can affect the surface behavior of DPPC/DPPG monolayers. Furthermore, the results obtained using mixed monolayer containing two major lung surfactants DPPC/DPPG and nanoparticles will be helpful for deep understanding the harm of PM2.5 to lung health.