DPPC Acyl Chains Research Articles

The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayers

Fipronil is a widely used commercial insecticide whose action mechanism consists in blocking the influx of chloride ions through the γ-aminobutyric acid type A receptor (GABAA-R), an integral membrane protein. The present study investigates the interaction of fipronil with phospholipid Langmuir monolayers, in order to characterize the effects that its partition could exert on the physical properties of these model membranes. A combined experimental and molecular dynamics (MD) simulations approach was performed. MD simulations were conducted in such a way that they resemble an experimental compression isotherm of DPPC in the presence of fipronil in the aqueous subphase. Both the experimental and the simulated compression isotherm showed that the partition of fipronil between DPPC molecules induces an expansion of the monolayer. Experimental results also showed that fipronil can penetrate lipid monolayers even in condensed packing states. MD simulations showed that fipronil induces an ordering effect in the acyl chains of DPPC in the liquid-condensed phase. In addition, the simulations indicate that fipronil orients parallel to the plane of the monolayer and that it establishes hydrogen bonds with the glycerol region of DPPC. Free energy profiles of the partition of fipronil into the monolayers, obtained by means of umbrella sampling, indicated that its penetration is thermodynamically favorable, being the interphase between the glycerol region and the acyl chains of DPPC its most favorable location. Our results suggest that fipronil could modulate the supramolecular organization of biological membranes surrounding GABAA-R, contributing, at least in part, to its action mechanism.

Skin permeation and thermodynamic features of curcumin-loaded liposomes.

This work describes the development of liposomes encapsulating curcumin (CURC) aiming to provide insights on the influence of CURC on the thermodynamic and skin permeation/penetration features of the vesicles. CURC-loaded liposomes were prepared by hydration of lipid film, in the 0.1-15% CURC:DPPC w/w ratio range. The obtained formulations were characterized for their size distribution, zeta potential and vesicle deformability, along with their thermodynamic properties and ex vivo skin penetration/permeation ability. Liposome size was 110-130 nm for all formulations, with fairly narrow size distribution (polydispersity index was ≤0.20) and a zeta potential mildly decreasing with CURC loading. DSC outcomes indicated that CURC interferes with the packing of DPPC acyl chains in liposome bilayer when CURC percentage was at least 10%, leading to a more fluid state than blank and low-payload vesicles. Consistently, the deformability index of liposomes with 15% CURC:DPPC was strongly increased compared to other formulations. This is congruent with ex vivo skin penetration/permeation results, which showed how more deformable liposomes showed an improved deposition in the epidermis, which acts as a reservoir for the active molecule. Altogether, results hint at a possible application of high payload liposomes for improved topical dermal accumulations of actives.

Licofelone-DPPC Interactions: Putting Membrane Lipids on the Radar of Drug Development.

(1) Background: Membrane lipids have been disregarded in drug development throughout the years. Recently, they gained attention in drug design as targets, but they are still disregarded in the latter stages. Thus, this study aims to highlight the relevance of considering membrane lipids in the preclinical phase of drug development. (2) Methods: The interactions of a drug candidate for clinical use (licofelone) with a membrane model system made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were evaluated by combining Langmuir isotherms, Brewster angle microscopy (BAM), polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS), and grazing-incidence X-ray diffraction (GIXD) measurements. (3) Results: Licofelone caused the expansion of the DPPC isotherm without changing the lipid phase transition profile. Moreover, licofelone induced the reduction of DPPC packing density, while increasing the local order of the DPPC acyl chains. (4) Conclusions: The licofelone-induced alterations in the structural organization of phosphatidylcholine monolayers may be related to its pharmacological actions. Thus, the combination of studying drug-membrane interactions with the pharmacological characterization that occurs in the preclinical stage may gather additional information about the mechanisms of action and toxicity of drug candidates. Ultimately, the addition of this innovative step shall improve the success rate of drug development.

Boundary lipids of the nicotinic acetylcholine receptor: Spontaneous partitioning via coarse-grained molecular dynamics simulation

Reconstituted nicotinic acetylcholine receptors (nAChRs) exhibit significant gain-of-function upon addition of cholesterol to reconstitution mixtures, and cholesterol affects the organization of nAChRs within domain-forming membranes, but whether nAChR partitions to cholesterol-rich liquid-ordered (“raft” or lo) domains or cholesterol-poor liquid-disordered (ldo) domains is unknown. We use coarse-grained molecular dynamics simulations to observe spontaneous interactions of cholesterol, saturated lipids, and polyunsaturated (PUFA) lipids with nAChRs. In binary Dipalmitoylphosphatidylcholine:Cholesterol (DPPC:CHOL) mixtures, both CHOL and DPPC acyl chains were observed spontaneously entering deep “non-annular” cavities in the nAChR TMD, particularly at the subunit interface and the β subunit center, facilitated by the low amino acid density in the cryo-EM structure of nAChR in a native membrane. Cholesterol was highly enriched in the annulus around the TMD, but this effect extended over (at most) 5–10 Å. In domain-forming ternary mixtures containing PUFAs, the presence of a single receptor did not significantly affect the likelihood of domain formation. nAChR partitioned to any cholesterol-poor ldo domain that was present, regardless of whether the ldo or lo domain lipids had PC or PE headgroups. Enrichment of PUFAs among boundary lipids was positively correlated with their propensity for demixing from cholesterol-rich phases. Long n-3 chains (tested here with Docosahexaenoic Acid, DHA) were highly enriched in annular and non-annular embedded sites, partially displacing cholesterol and completely displacing DPPC, and occupying sites even deeper within the bundle. Shorter n-6 chains were far less effective at displacing cholesterol from non-annular sites.

Raman Spectroscopy Reveals Selective Interactions of Cytochrome c with Cardiolipin That Correlate with Membrane Permeability

Permeabilization of the outer mitochondrial membrane is an integral step in apoptosis. The resulting release of pro-apoptotic signaling proteins leads to cell destruction through activation of the cysteine-aspartic protease (caspase) cascade. However, the mechanism of outer mitochondrial membrane (OMM) permeabilization remains unclear. It was recently shown that cytochrome c can induce pore formation in cardiolipin-containing phospholipid membranes, leading to large dextran and protein permeability. In this work, the interaction of cytochrome c with cardiolipin-containing phospholipid vesicles, serving as models of the OMM, is investigated to probe cytochrome c-induced permeability. Lipid vesicles having either a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or mixed-DPPC/cardiolipin membrane and containing a membrane-impermeable Raman tracer 3-nitrobenzenesulfonate (3-NBS) were optically trapped, translated into a solution containing cytochrome c, and monitored for 3-NBS leakage. Cytochrome-correlated leakage was observed only in cardiolipin-containing vesicles. Structural changes observed in the Raman spectra during permeabilization indicated acyl chain disordering along with decreased intensity of the cardiolipin cis-double-bond stretching modes. When the vesicle-associated cytochrome c Raman spectrum is compared with a spectrum in buffer, heme-resonance bands are absent, indicating loss of Met-80 coordination. To verify selective interactions of cytochrome c with cardiolipin, these experiments were repeated where the DPPC acyl chains were deuterated (D62-DPPC), allowing spectral resolution of the DPPC acyl chain response from that of cardiolipin. Interestingly, D62-DPPC acyl chains were unaffected by cytochrome c accumulation, while cardiolipin showed major changes in acyl chain structure. These results suggest that cytochrome-induced permeabilization proceeds through selective interaction of cytochrome c with cardiolipin, resulting in protein unfolding, where the unfolded form interacts with cardiolipin acyl chains within the bilayer to induce permeability.

Sterol-Phospholipid Hybrids at the Air/Water Interface: Studies on Properties and Interactions with Parent Lipid Molecules.

The two synthetic sterol-phospholipid hybrids DCholPC and PCholPC were investigated in monolayers at the air/water interface. Study was based on π-A isotherm analysis complemented with application of grazing incidence X-ray diffraction. It was found that both compounds are capable of forming stable, highly condensed monolayers of a surface characteristics typical for sterols. GIXD studies show that the crystallographic area for DCholPC monolayer is very similar to that found for cholesterol (37.1 vs 38.0 Å(2)), while for PCholPC (28.8 Å(2)) it is significantly smaller as compared to area for the mixed Chol/DPPC 2/1 monolayer (33.4 Å(2)). In our study the problem of interactions between investigated sterol-phospholipid hybrids and natural membrane lipid components was for the first time analyzed in planar lipid systems. Studies on mixed monolayers showed that both hybrids, similarly to cholesterol, reveal a condensing effect toward DPPC acyl chains; however, DCholPC having two steroid moieties in the molecule was found to be more efficient. On the other hand, the sterol moiety and the hydrocarbon chain of PCholPC molecule are packed in the 2D crystalline phase extremely tight. Our studies showed that the investigated compounds can be applied as biocompatible components of stable liposomes.

CoenzymeQ10 localizations in model membranes. A Langmuir monolayer study

The interaction of coenzyme Q10 (CoQ10) in a monolayer of 1,2-dipalmitoyl-sn-glysero-3-phospho-L-choline (DPPC), in a monolayer of 1,2-dierucoyl-sn-glysero-3-phospho-L-choline (DEPC), in a monolayer of 1-palmitoyl-2-oleoyl-sn-glysero-3-phospho-L-serine (POPS) and in a monolayer of total lipid extract from pig brain (PB) has been investigated by using the Langmuir monolayer technique. Surface pressure (π)-mean molecular area (mma) isotherms have been measured for pure lipid monolayers and lipid monolayers with 0.5, 1.0, 2.0, 5.0 and 10.0 mol% CoQ10 concentrations. At the biological concentration (1.0-3.0 mol%) of CoQ10, intercalation of CoQ10 occurs in the lipid acyl chains of DPPC, POPS and PB monolayers. Above the biological concentration of CoQ10, the CoQ10 molecule induces domain formation in the monolayers of DPPC, POPS and PB lipids. The DEPC monolayer behavior deviates from the other lipids in this study. At 2.0 mol% the CoQ10 promotes very dense lipid packing, and the CoQ10 molecule is located parallel to the DEPC acyl chains at all concentrations.

Competitive molecular interaction among paeonol-loaded liposomes: Differential scanning calorimetry and synchrotron X-ray diffraction studies

Thermotropic phase behavior of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes containing 5 mol% cholesterol, or 5 mol% stigmasterol, or 5 mol% paeonol have been investigated by differential scanning calorimetry (DSC) and synchrotron X-ray diffraction (XRD) techniques, to investigate the competitive molecular interaction among paeonol-loaded liposomes. The results show that both sterol and paeonol can incorporate into hydrophobic region and interact with acyl chains of DPPC. Both 5 mol% sterols and 5 mol% paeonol can promote the formation of rippled gel phase of DPPC liposomes at room temperature. 5 mol% paeonol can induce the occurrence of phase separation in DPPC liposomes, but 5 mol% cholesterol or 5 mol% stigmasterol cannot induce this phenomenon. Both the repeat distance and the correlation length of paeonol-poor domain are larger than those of coexisted paeonol-rich domain. Both calorimetric data and SAXS patterns show that sterols have more favorable, stabilizing interactions with DPPC than paeonol, implying that high concentrations of sterols will have a negative effect on the loading of paeonol. In addition, calorimetric data show that cholesterol have a little more favorable, stabilizing interactions with DPPC than stigmasterol. The results of this study will play an important role in optimizing the formulation of paeonol-loaded liposomes.

Fluorescence and thermotropic studies of the interactions of PEI-cholesterol based PEI-chol lipopolymers with dipalmitoyl phosphatidylcholine membranes

Numerous PEI derived polymers have been explored for their use in gene delivery. Nine PEI-chol lipopolymers based on cholesterol grafting on three polyethyleneimines (PEI) of different molecular weights have been synthesized. Firstly their aggregation behavior has been studied using transmission electron microscopy and then their interactions with l-α-dipalmitoyl phosphatidylcholine (DPPC) membranes have been examined using fluorescence anisotropy and differential scanning calorimetry (DSC). These PEI-chol lipopolymers are found to quench the chain motion of the acyl chains of DPPC, when incorporated in membranes, depending upon the cholesterol grafting on PEI. These PEI-chol lipopolymers act as filler molecules in membranes. Electron microscopy shows the different aggregation behavior of these new PEI-chol lipopolymers depending upon the molecular weight of PEI and percentage of cholesterol grafting. Detailed analysis of the fluorescence anisotropy and DSC data indicate that the nature of perturbation induced by PEI-chol lipopolymers is dependent upon the molecular weight of the PEI used and the % of cholesterol grafting on PEI. In general, PEI-chol lipopolymers rigidify the liquid-crystalline phase of the membranes without any noticeable effect on the gel phase unlike natural cholesterol, which is known to fluidize the gel phase of the membranes.

Temperature Dependence of the Phospholipids Bilayers Stability, Studied by FTIR Spectroscopy

The temperature induced modifications in the lipid bilayers in water were studied by using 2D-FTIR Correlation Spectroscopy. The spectral range analysed in this paper corresponds to symmetric and asymmetric stretching vibrations of the �CH2 groups from the acyl chains of DPPC. Autocorrelation peaks at 2916 cm-1 and 2848.5 cm-1 and asynchrone modifications in the spectral ranges 2916-3000 cm-1 and 2848-3000 cm-1 were evidenced. The revealed modifications indicate changes in the conformers of the hydrocarbon chains in the phase transition from the gel to liquid crystalline phases, as well as the variations in the concentration of the two phases with temperature increasing.

Effects of fluorescent probe NBD-PC on the structure, dynamics and phase transition of DPPC. A molecular dynamics and differential scanning calorimetry study

We present a combined theoretical (molecular dynamics, MD) and experimental (differential scanning calorimetry, DSC) study of the effect of 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) acyl chain-labeled fluorescent phospholipid analogs (C6-NBD-PC and C12-NBD-PC) on 1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC) bilayers. DSC measurements reveal that < 1 mol% of NBD-PC causes elimination of the pre-transition and a large loss of cooperativity of the main transition of DPPC. Labeling with C6-NBD-PC or C12-NBD-PC shifts the main transition temperature to lower or higher values, respectively. Following our recent report on the location and dynamics of these probes ( BBA 1768 (2007) 467–478) in fluid phase DPPC, we present a detailed analysis of 100-ns MD simulations of systems containing either C6-NBD-PC or C12-NBD-PC, focused on their influence on several properties of the host bilayer. Whereas most monitored parameters are not severely affected for 1.6 mol% of probe, for the higher concentration studied (6.2 mol%) important differences are evident. In agreement with published reports, we observed that the average area per phospholipid molecule increases, whereas DPPC acyl chain order parameters decrease. Moreover, we predict that incorporation of NBD-PC should increase the electrostatic potential across the bilayer and, especially for C12-NBD-PC, slow lateral diffusion of DPPC molecules and rotational mobility of DPPC acyl chains.

Interaction of Ovalbumin with Phospholipids Langmuir−Blodgett Film

Interaction of native ovalbumin (OVA) with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) Langmuir-Blodgett monolayer has been studied at the air-water interface. A compressibility study shows the positive association with DPPC. Adsorption kinetics shows that the protein adsorption is a one-step process and the amount of protein adsorbed depends on the concentration of protein at the water subphase. Incorporation of protein into the DPPC layer is surface-pressure dependent. The compressibility study indicates that the DPPC-OVA interaction is hydrophobic in nature and structural reorganization is eminent to adjust the hydrophobic mismatch between DPPC acyl chains and OVA hydrophobic moieties. At higher pressure, OVA tends to squeeze out from the DPPC monolayer. A nanometer scale FE-SEM image confirms this observation. Globular aggregates of protein of dimension 60-80 nm were observed in DPPC-OVA supported film. Steady-state fluorescence spectroscopy suggests that the tryptophan residues of OVA are main emitting species. The blue shift of tryptophan fluorescence in supported film may be due to the tryptophan molecule of protein exposed to the hydrophobic air phase.

Raman and Fourier transform infrared study of phytol effects on saturated and unsaturated lipid multibilayers

AbstractThe effects of phytol on DPPC and OPPC multilayers were investigated using FT‐IR and Raman spectroscopy. The results were compared with those obtained with α‐tocopherol (α‐T) and α‐tocopherol acetate (α‐TA). The chain packing was analyzed using Raman intensity ratios measured in the CH2 stretching region, whereas the number of gauche bonds introduced by phytol was estimated by the measure of the FT‐IR absorbance of the CH2 wagging progression modes. It is shown that the chain packing is reduced and that gauche rotamer formation is promoted by phytol in the gel phase. Phytol has a very similar effect on the acyl chains of DPPC to α‐T but does not have the same impact on the CO stretching vibrations of this lipid. The results indicate that phytol perturbs the interfacial region of DPPC causing dehydration or a conformational modification of the ester groups. Furthermore, the modification of the OPPC chain order induced by phytol is slightly different with respect to α‐T. It is concluded that (1) a hydrogen bond between the hydroxyl group of α‐T and the phospholipid carbonyl groups may not necessarily be associated with the stabilization of the membrane, (2) the studied phytyl compounds may be located more or less close to the membrane interface, (3) the presence of the chromanol ring may strongly influence the location of vitamin E within the membrane and, consequently, its capacity to catch free radicals and (4) the hydroxyl group, chroman moiety and phytyl chain all play a crucial role that determines the effects of α‐T on lipid acyl chains and its location within membranes, which in turn can affect its biological function. Copyright © 2002 John Wiley &amp; Sons, Ltd.

Thermal Lipid Order−Disorder Transitions in Mixtures of Cationic Cholesteryl Lipid Analogues and Dipalmitoyl Phosphatidylcholine Membranes

Two types of cationic cholesteryl amphiphiles, one where the headgroup is attached to the steroid by an ester linkage and the second by an ether linkage, were synthesized. A third type of cholesteryl lipid bearing an oligoethylene glycol segment was also prepared. Each of these synthetic lipids generated vesicle-like aggregates with closed inner aqueous compartments from their aqueous suspensions. We examined their interaction with L-α-dipalmitoyl phosphatidylcholine (DPPC) membranes using fluorescence anisotropy, transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). When included in membranes, the synthetic cholesteryl lipids were found to quench the chain motion of the acyl chains of DPPC. This suggests that these cationic cholesteryl derivatives act as filler molecules despite modification at the headgroup level from the molecular structure of natural cholesterol. Careful analyses of DSC and fluorescence anisotropy data suggest that the nature of perturbation induced by each of these cationic cholesterol derivatives is dependent on the details of their molecular structure and provides significant information on the nature of interaction of these derivatives with phospholipid molecules. In general, amphiphiles that support structured water at the interfacial region tend to rigidify the fluid phase more than others. Importantly, these cholesteryl amphiphiles behave less like cholesterol in that their incorporation in DPPC not only abolishes the phase transition but also depresses the phase transition temperature.

Influence of the glycopeptidic moiety of mycobacterial glycopeptidolipids on their lateral organization in phospholipid monolayers

Glycopeptidolipids (GPLs) from the cell wall of opportunistic pathogenic mycobacteria are potential factors of pathogenicity which can interact with biological membranes. GPL suspensions uncouple oxidative phosphorylation of mitochondria and increase membrane permeability of liposomes. Heavily glycosylated GPLs are less active than lightly glycosylated ones. GPL–phospholipid interactions into preformed mixed films at the air–water interface were investigated in order to understand the permeabilization efficiency differences among GPLs. Polarization modulation infrared reflection absorption spectroscopy (PMIRRAS) was used to determine, in situ, the organization of GPL and of 1,2-di(perdeuteropalmitoyl)phosphatidylcholine (DPPC) molecules in mixed films. Compression isotherms of GPL alone or mixed with DPPC in various proportions showed that the less the GPL was glycosylated the higher its miscibility with DPPC. PMIRRAS studies indicated that low miscibility may result from large self-association of GPL molecules in β-sheet structures. Low glycosylated GPL molecules increased disorder of DPPC acyl chains. Based on these results, an explanatory model is proposed for membrane permeabilization. Increase of passive permeability may arise from disruption of phospholipid packing induced by GPL molecules. GPL segregation is proposed as the cause of low activity of GPL with high sugar content, by decreasing the number of GPL molecules interacting with phospholipids.

Effect of water on lamellar structure of DPPC/sugar systems

The ability of two monosaccharides, four disaccharides and one trisaccharide, to lower the transition temperature of l-α-dipalmitoyl phosphatidylcholine (DPPC) was investigated using differential scanning calorimetry (DSC) and the ability of these sugars to change the lateral packing of the acyl chains of DPPC was investigated using wide-angle X-ray diffraction. The sugars affected the gel–liquid crystal transition temperature ( T c) of DPPC when the water content of the DPPC/sugar systems was less than 20 wt.%. Specifically, T c of the DPPC without sugar increased to approximately 106°C, the T c of the DPPC/monosaccharide system remained almost constant at 43°C and of the DPPC/disaccharide or trisaccharide systems decreased to approximately 24°C. In the dehydrated state, di- and trisaccharides caused looser packing of the DPPC hydrocarbon chains than the monosaccharides did, and the sugars affected the packing mode in different ways. The addition of water caused this difference in the sugars' effects on the packing mode to disappear and further addition of water caused the effect of sugar to almost disappear. Thus, the addition of water to a DPPC/sugar system weakens the interaction between the sugar and lipid and strengthens the DPPC chain packing.

Pulmonary lung surfactant synthetic peptide concentration-dependent modulation of DPPC and POPG acyl chain order in a DPPC:POPG:palmitic acid lipid mixture

Lung surfactant-associated protein interaction with lipid matrices and the effects on lipid thermotropic phase behavior are areas of active research. Many studies limit the lipids to a single or two-component system. The current investigation utilizes a three-lipid component matrix (DPPC:POPG:palmitic acid) to investigate the impact of a synthetic surfactant protein B fragment (SP-B 53ndash;78 DiACM) on the dynamic surface activity of the lipid admixture as measured by a Wilhelmy surface balance. Also, the modulation of the individual lipid acyl chain order by the peptide within the lipid matrix is studied through the use of thermal perturbation FTIR spectroscopy. The data clearly demonstrate a concentration-dependent effect of the peptide on the surface activity with an improvement in the dynamic surface tension diagram characteristics (decreased surface tension and increased collapse plateau) especially at low, 0.36 M%, peptide concentrations. These effects are diminished upon further addition of the peptide. FTIR spectral data demonstrate that the peptide addition results in a significant increase in the acyl chain order of the DPPC and POPG components as measured by the position of the methylene stretching vibrational bands. DPPC is most sensitive to the peptide presence, while the palmitic acid is least affected. The transition temperatures of the individual lipids are also increased with the addition of the peptide. The presence of POPG in the matrix achieves the surface activity similarly seen with natural lung surfactant relative to a DPPC/palmitic acid lipid matrix alone. Its presence increases the sensitivity of the DPPC acyl chains to the presence of the peptide. These effects on the chain order are most probably related to the increased acyl chain fluidity which POPG imparts to the lipid matrix because of the presence of the cis double bond. The phosphatidylglycerol headgroup also adds a negative charge to the lipid matrix which enhances the peptidelipid interaction. Although the palmitic acid is minimally affected by the peptide, its presence, as suggested by surface balance measurements, results in the establishment of a stable lipid film with DPPC, capable of achieving low surface tension values.

Raman spectroscopic study of boundary lipid in 1,2-dipalmitoylphosphatidylcholine/apolipoprotein A—I recombinants

Raman spectroscopy has been used to obtain thermal phase transition profiles for recombinant particles composed of 1,2-dipalmitoylphosphatidylcholine (DPPC) and apolipoprotein A—I. Comparison of these profiles with unilamellar vesicles of DPPC indicates that lateral packing of DPPC acyl chains is tighter in recombinant DPPC/apolipoporotein A—I particles than in uncomplexed lipid of unilamellar vesicles. Consequently, the magnitude of the entropy change associated with acyl chain melting in the recombinants at the main lipid phase transition is almost twice that of unilamellar DPPC. In addition, a second phase transition has been observed for the DPPC/apolipoprotein A—I complex and has been assigned to the acyl chain melting of DPPC molecules which are bound to the apolipoprotein annulus on the periphery of the discoidal complexes. A combination of results from Raman spectroscopy, electron micrograph measurements and chemical analysis leads to the conclusion that these protein-bound lipids, the “boundary layer”, account for about 20% of the total lipid in the recombinant material. Calculations indicate that there are about 55 protein-bound lipid molecules per apolipoprotein A—I molecule in the DPPC/apolipoprotein A—I discoidal complexes prepared for this study.

Cholesterol interactions with tetracosenoic acid phospholipids in model cell membranes: role of the double-bond position

The synthesis and thermotropic properties of 1,2-di-(9Z)-9-tetracosenoylphosphatidylcholine [delta 9-PC(24:1,24:1), 1], 1,2-di-(5Z)-5-tetracosenoylphosphatidylcholine [delta 5-PC(24:1,24:1), 2], and 1,2-di-(15Z)-15- tetracosenoylphosphatidylcholine [delta 15-PC(24:1,24:1), 3] are reported. Liposomes prepared from these phospholipids differ from those of the natural sponge phospholipids, 1,2-di-(5Z,9Z)-5,9-hexacosadienoylphosphatidylcholine (4a) and the corresponding ethanolamine (4b), both of which virtually exclude cholesterol from their bilayers. The behavior of 1 and 2 is similar to that of 1,2-di-(6Z,9Z)-6,9-hexacosadienoylphosphatidylcholine (5), which exhibits a partial molecular interaction with cholesterol. In the case of 3, cholesterol appears to interact with the saturated acyl chain regions of this phospholipid in a manner similar to that of its interaction with DPPC acyl chains. This study delineates the effect of the double-bond location in long fatty acyl chains of phospholipids on their interactions with cholesterol.