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PubMed1986

The use of different lipids to express serum tocopherol: lipid ratios for the measurement of vitamin E status.

Plasma tocopherol was measured in 85 alcoholic patients and 40 control subjects from a local factory. Cholesterol, triglycerides and phospholipids were measured individually and summed to give an estimate of total serum lipids. Plasma tocopherol concentrations of the alcoholics were significantly lower than those of the controls and showed wide variation from marked deficiency to the upper limit of the normal range. Using regression analysis, 1.11 mumol tocopherol/mmol total lipids were calculated as the threshold of deficiency equivalent to 0.8 mg tocopherol/g total lipid established by Horwitt et al. The sensitivity and specificity of other tocopherol:lipid ratios for identifying vitamin E deficiency was compared with the tocopherol:total lipid ratio. Thresholds of deficiency for the different tocopherol:lipid ratios were calculated. The tocopherol:cholesterol+triglyceride ratio was found to be almost as powerful in identifying vitamin E deficiency as the tocopherol:total lipid ratio (sensitivity 95%, specificity 99%). Of the tocopherol:individual lipid ratios, the tocopherol:cholesterol ratio gave the best results (sensitivity 86%, specificity 94%).

Alcoholism↗
PubMed2005

Lipid mixtures prepared with well-defined synthetic ceramides closely mimic the unique stratum corneum lipid phase behavior.

Lipid lamellae present in the outermost layer of the skin, the stratum corneum, form the main barrier for the diffusion of molecules through the skin. The presence of a unique 13 nm lamellar phase and its high crystallinity are characteristic for the stratum corneum lipid phase behavior. In the present study, small-angle and wide-angle X-ray diffraction were used to examine the organization in lipid mixtures prepared with a unique set of well-defined synthetic ceramides, varying from each other in head group architecture and acyl chain length. The results show that equimolar mixtures of cholesterol, free fatty acids, and synthetic ceramides (resembling the composition of pig ceramides) closely resemble the lamellar and lateral stratum corneum lipid organization, both at room and higher temperatures. Exclusion of several ceramide classes from the mixture does not affect the lipid organization. However, complete substitution of ceramide 1 (acylceramide with a sphingosine base) with ceramide 9 (acylceramide with a phytosphingosine base) reduces the formation of the long periodicity lamellar phase. This indicates that the head group architecture of acylceramides affects the lipid organization. In conclusion, lipid mixtures prepared with well-defined synthetic ceramides offer an attractive tool with which to unravel the importance of the molecular structure of individual ceramides for proper lipid organization.

Ceramides↗
PubMed2005

Give lipids a START: the StAR-related lipid transfer (START) domain in mammals.

The steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain is a protein module of approximately 210 residues that binds lipids, including sterols. Fifteen mammalian proteins, STARD1-STARD15, possess a START domain and these can be grouped into six subfamilies. Cholesterol, 25-hydroxycholesterol, phosphatidylcholine, phosphatidylethanolamine and ceramides are ligands for STARD1/STARD3/STARD5, STARD5, STARD2/STARD10, STARD10 and STARD11, respectively. The lipids or sterols bound by the remaining 9 START proteins are unknown. Recent studies show that the C-terminal end of the domain plays a fundamental role, forming a lid over a deep lipid-binding pocket that shields the ligand from the external environment. The START domain can be regarded as a lipid-exchange and/or a lipid-sensing domain. Mammalian START proteins have diverse expression patterns and can be found free in the cytoplasm, attached to membranes or in the nucleus. They appear to function in a variety of distinct physiological processes, such as lipid transfer between intracellular compartments, lipid metabolism and modulation of signaling events. Mutation or misexpression of START proteins is linked to pathological processes, including genetic disorders, autoimmune disease and cancer.

Animals↗
PubMedDate not supplied

Serum lipids during parenteral nutrition with a 10% lipid emulsion with reduced phopholipid emulsifier content in premature infants.

Fourteen premature infants (range 26 + 0 to 32 + 3), all but two appropriate for gestational age with a mean body weight of 1196 g (range 860 to 2770 g) received a 10% lipid emulsion. This lipid emulsion contained half of the formerly used phospholipid emulsifier concentration reducing the phospholipid/triglyceride ratio to the ratio used for the 20% lipid emulsion (0.06 instead of 0.12). Lipid emulsion was given over a 10 day period commencing at the third day of life with 0.5 g/kg/24 h which was increased daily up to a dose of 2.0-2.5 g/kg/24 h which was reached in all patients at the seventh day of the observation period. During this time mean serum concentrations of cholesterol increased non-significantly from 76.1 mg/dl (SD 33.7) before lipid emulsion to 86.1 mg/dl (SD 36.4) on day seven of the observation period. 13 of the 14 patients (97%) showed no pathological increase of their serum triglyceride concentration during lipid infusion. Mean serum triglyceride concentration increased from 65.3 mg/dl (SD 32.0 mg/dl) before the start of lipid emulsion to 102.6 mg/dl (SD 76.5) on day four (p < 0.05) but with no further significant increase. Lipid emulsions with 10% triglyceride but lower phospholipid content are tolerated without pathological increase in triglyceride or cholesterol serum concentration in the vast majority of premature newborns.

Cholesterol↗
PubMed1977

Growth and liver lipids of casein-fed rats incubated in the presence of glucose and lipid.

The effect of casein that has reacted with glucose and/or lipid on the growth and hepatic lipids of rats was studied. A mixture of casein-ethyl linoleate-glucose was kept at 50 degrees C and RH 80.4% for 14 days and defatted with ethyl ether and acetone. When the casein that had reacted with glucose and lipid was fed at at 10% dietary level for 14 days, the growth of rats was markedly depressed. Not only levels of hepatic lipids but also of plasma lipids were specifically modified. The accumulation of hepatic lipids was primarily due to the increase in triglyceride. When casein was reacted with glucose alone, similar but considerably lesser changes in the growth and liver lipid components were observed. These data indicate that casein characteristically deteriorates with glucose and/or lipid, but the effect of oxidation of the latter is very remarkable.

Animals↗
PubMed2001

A proteolytic method for distinguishing between lipid-free and lipid-bound apolipoprotein A-I.

Recent studies indicate that certain lipid-poor forms of apolipoprotein (apo)A-I may be particularly important in promoting cholesterol release from overburdened cells in the periphery. However, a detailed understanding of the physiological relevance of these species has been hampered by the difficulty in measuring them. As part of a search for a rapid assay for these forms of apoA-I, we have observed that the protease enteropeptidase can specifically cleave human lipid-free apoA-I but not its lipid-bound form. Enteropeptidase cleaved lipid-free apoA-I at a single site at amino acid 188, resulting in an N-terminal fragment of 22 kDa. However, apoA-I was not susceptible to enteropeptidase when present in reconstituted high-density lipoprotein (rHDL) particles as small as 6 nm in diameter or in human HDL(3) particles, even at extremely high enzyme-to-protein ratios and extended reaction times. We capitalized on this observation to develop an assay for the measurement of lipid-poor apoA-I in in vitro systems. Densitometry was used to generate a standard curve from sodium dodecyl sulfate polyacrylamide gels to determine the amounts of the N-terminal proteolytic fragment in unknown samples treated with enteropeptidase. This system could accurately quantify apoA-I that had been displaced from rHDL particles and human HDL(3) with purified apoA-II. On the basis of the results, a system of nomenclature is proposed for "lipid-free," "lipid-poor," and "lipid bound" apoA-I. The reported method distinguishes forms of apoA-I by a conformational parameter without previous separation of the species. This simple and inexpensive method will be useful for understanding the characteristics of plasma HDL that are favorable for the dissociation of apoA-I.

Apolipoprotein A-I↗
PubMed2002

Nuclear magnetic resonance-visible lipids induced by cationic lipophilic chemotherapeutic agents are accompanied by increased lipid droplet formation and damaged mitochondria.

Proton nuclear magnetic resonance (NMR) spectroscopy, histological lipid staining, and electron microscopy were used to assess the biochemical and structural changes induced by treating the cultured human breast cell line HBL-100 with the cationic lipophilic phosphonium salts p-(triphenylphosphoniummethyl) benzaldehyde chloride (drug A) and [4-(hydrazinocarboxy)-1-butyl] tris-(4-dimethylaminophenyl) phosphonium chloride (drug B). The major biochemical change detected by (1)H NMR in drug-treated cells was a significant time- and concentration-dependent increase in lipid acyl chain resonances arising from mobile lipids. The amount of NMR-visible lipid strongly correlated with morphometric measurements of oil red O-staining lipid detected in the cytoplasm by light microscopy. Ultrastructural investigations revealed substantial damage to mitochondria and the progressive development of lipid droplets accompanied by end-stage autophagic vacuoles, in the form of densely staining myelinoid bodies, after treatment of HBL-100 cells with drug B at the IC(50). No apparent increase in acid phosphatase activity was observed using electron microscopy, indicating that the accumulation of phospholipids in myelinoid bodies may result from substrate inundation of the lysosome, rather than increased lysosomal activity. These results indicate a potential role for lysosomal lipid catabolism in the formation of NMR-visible lipids in models of cytotoxic insult.

Antineoplastic Agents↗
PubMed1992

The lipid-binding peptide from the plasma membrane Ca2+ pump binds calmodulin, and the primary calmodulin-binding domain interacts with lipid.

Peptide G25 (KKAVKVPKKEKSVLQGKLTRLAVQI) representing the putative lipid-binding region (G region) of the erythrocyte Ca2+ pump was synthesized. This peptide interacted with acidic lipids, as shown by the increase in size of phosphatidylserine liposomes in its presence. This lipid interaction is consistent with the previous evidence suggesting that the portion of the pump from which this peptide was taken is responsible for the activation of the pump by acidic lipid. G25 also bound to calmodulin, as was shown by its cause of a shift in the fluorescence of 5-dimethylamino naphthalene-1-sulfonyl- (dansyl)-calmodulin, and by its competition with Ca2+ pump for calmodulin. Its Kd for dansyl-calmodulin was much higher (0.8 microM) than that of the peptides representing the primary calmodulin-binding region (C region) of the Ca2+ pump. Although the presence of the G region provided the possibility of a second calmodulin-binding site, activation of the pump by calmodulin always could be fitted by simple saturation kinetics. The calmodulin-binding peptide from the C region of the pump, C28R2, also interacted with lipid with even greater effectiveness than G25. When the C region of the pump was saturated with calmodulin, acidic lipid activation of the pump followed simple saturation kinetics. However, when calmodulin was omitted, a higher concentration of lipid was needed for saturation and the kinetics became complex. The data are consistent with the idea that calmodulin activates the pump only by interaction at the C region, but that acidic lipid activates by interaction at both of the C and G regions.

Animals↗
PubMed1992

Membrane lipid modification and sensitivity of leukemic cells to the thioether lipid analogue BM 41.440.

Since the ether lipid anticancer drugs are membrane targeted, we examined the effect of membrane lipid structural alteration on their cytotoxicity. Enrichment with docosahexaenoic acid increased the sensitivity to the thioether lipid BM 41.440, compared to control cells enriched with oleic acid. The effect was dependent upon drug concentration, time, and the extent of cellular fatty acid enrichment. Other polyunsaturated fatty acids had a similar effect, which was proportional to the degree of unsaturation of the molecule inserted. Depletion of cellular glutathione with buthionine sulfoximine increased the sensitivity to ether lipid, but prooxidants such as Fe2+ and antioxidants such as vitamin E had little effect. The addition of serum to the incubation medium markedly diminished the cytotoxicity of ether lipids for cells modified with both docosahexaenoic acid and oleic acid, probably due to binding of the drug to serum components. The toxicity of another ether lipid, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine, was not affected appreciably by membrane alteration. Drug uptake studies with a radiolabeled BM 41.440 analogue, 1-[3H]hexadecylthio-2-ethyl-rac- glycero-3-phosphocholine, demonstrated no difference in transport at early time points and no difference in accumulation up to 60 min. We conclude that increases in cellular and/or membrane fatty acid polyunsaturation heighten the cytotoxic effect of a membrane-active ether lipid. The effect is not due to a change in drug transport or accumulation. It may be related to a change in oxidative events. These observations provide further confirmation of the membrane being the target of ether lipid action, using biochemical rather than morphological techniques. Most importantly, this observation offers a potential innovative approach to therapy.

Animals↗
PubMed1992

Inhibition of endotoxin or lipid A-induced tumor necrosis factor production by synthetic lipid A partial structures in human peripheral blood mononuclear cells.

Most of the toxic reactions during Gram-negative infections are mediated by inflammatory cytokines induced by endotoxin, also termed lipopolysaccharide (LPS). To evaluate the possibility of synthetic derivatives of LPS to antagonize endotoxin-mediated activities, we have examined the effect of synthetic lipid A partial structures, precursor Ia (compound 406 or LA-14-PP) and lipid X (compound 401) on in vitro LPS or lipid A-induced release of tumor necrosis factor (TNF) by human peripheral blood mononuclear cells. In agreement with previous reports it was shown that LPS of Salmonella abortus equi and synthetic Escherichia coli-type lipid A (compound 506 or LA-15-PP) have potent TNF-inducing capacity. The maximum release of TNF was found after stimulation with 1 to 10 ng/ml of LPS or 10 to 1000 ng/ml of lipid A. Synthetic precursor Ia and lipid X failed to induce TNF release, but could inhibit LPS or lipid A-induced TNF release in a dose-dependent manner. Inhibition was not due to a shift of the kinetic of cytokine release, and was observed in the early stage of TNF production. Moreover, we found that the synergistic effect of interferon-gamma with LPS in induction of TNF release could also be counteracted by the addition of synthetic precursor Ia. The observation that precursor Ia failed to inhibit the induction of TNF by Bacillus Calmette-Guérin, Staphylococcus aureus cowan I or lipopeptide indicated that specific mechanisms are involved in suppression by lipid A partial structures on LPS-induced cytokine production.(ABSTRACT TRUNCATED AT 250 WORDS)

Endotoxins↗
PubMed2006

Solid lipid nanoparticles (SLN)--effects of lipid composition on in vitro degradation and in vivo toxicity.

Solid lipid nanoparticles (SLN) composed of two different lipid matrices were produced to assess their in vivo toxicity in mice. Matrix substances were (i) Compritol (glycerol behenate), a physiological lipid with GRAS status (generally recognized as safe [FDA]), and (ii) cetyl palmitate, a less physiological compound. Physicochemical data proved the suitability of SLN batches for intravenous administration. To assess the in vivo toxicity of produced batches, 400 microl SLN dispersion (lipid content 10% [m/m]) were administered to mice via a bolus injection for six times within a period of 20 days (high dose administration). Additionally, a multiple low dose administration was performed with Compritol-SLN as well (200 microl SLN dispersion, lipid content 2.5% [m/m]). Hepatic and splenic tissues were analysed histologically. In vivo results were dependent on the lipid matrix, as well as on the dose administered. For cetyl palmitate containing SLN no pathological results were obtained, while high dosed Compritol containing formulations led to accumulation of the lipid in liver and spleen and subsequently to pathological alterations. These alterations were found to be partially reversible within six weeks after completing intravenous administration. Liver architecture was nearly recovered. In contrast, low dosed Compritol SLN were well tolerated. Lipid accumulation and pathological alterations of high dosed Compritol SLN were attributed to the slow degradation of the Compritol matrix which could be shown by performing in vitro studies in human plasma.

Animals↗
PubMedDate not supplied

Biologically active ether lipids: incorporation of long-chain precursors into 1(3),2-diacylglycero-3(1)-O-4'-(N,N,N-trimethyl)homoserines and other lipids of Chlorella fusca.

The lipids of Chlorella fusca are composed of the ester lipids typical of photosynthetically active cells. In addition, there occurs a class of less common ether lipids, the biologically active 1(3),2-diacylglycero-3(1)-O-4'-(N,N,N- trimethyl)homoserines, at a level of about 1.3% of total lipids. The acyl moieties of the total lipids include saturated as well as mono-, di- and tri-unsaturated species with chain lengths of 16 and 18 carbon atoms, the major constituents being palmitic and oleic acids. In both the diacylglycerophosphocholines, i.e., the major class of ester phospholipids, and the diacylglycero-4'-O-(N,N,N-trimethyl)homoserines palmitic acid is located predominantly at position 1 of the glycerol backbone, whereas oleic acid is almost equally distributed between positions 1 and 2; palmitoleic and polyunsaturated fatty acids are esterified preferentially at position 2. Incubation of C. fusca cultures with 14C-labeled fatty acids leads to their rapid incorporation into various lipid classes. Oleic and palmitic acids are incorporated at a faster rate than stearic acid (18:1 greater than 16:0 much greater than 18:0). 1,2- and 1,3-Diacylglycerols are the most prominent intermediates of early metabolism of the exogenous fatty acids. In the course of time, a steady decrease of radioactive 1,2-diacylglycerols is observed that is accompanied by an increase in labeled triacylglycerols, diacylglycerophosphocholines, and diacylglycero-O-(N,N,N-trimethyl)homoserines. The stereospecific distribution of acyl moieties in the diacylglycero-O-(N,N,N-trimethyl)homoserines in C. fusca indicates that these ether lipids are derived from 1,2-diacylglycerol intermediates. This notion is supported by the finding that during incubation with radioactively labeled fatty acids the formation of diacylglycero-O-(N,N,N-trimethyl)homoserines parallels the biosynthesis of both diacylglycerophosphocholines and diacylglycerophosphoethanolamines, two classes of phospholipids which are known to be derived from 1,2-diacylglycerols. The mechanism of the formation of the ether bond, however, is as yet unknown. Incubation of C. fusca cultures with 14C-labeled fatty acids or alcohols leads to the formation of fair proportions of wax esters that are labeled in both the acyl and the alkyl moieties, indicating that in these algae fatty acids and alcohols are interconverted. 14C-Labeled long-chain alcohols are not incorporated into the alkyl moieties of ether lipids, whereas labeled 1-O-alkylglycerols are used, though to a very small extent, as precursors of ether phospholipids.

Chlorella↗
PubMed1986

Effects of PUVA therapy on skin surface lipids: skin surface lipid peroxidation in psoriasis vulgaris and its biological significance.

PUVA therapy (Psoralen + UVA irradiation) is an effective mode of photochemotherapy for psoriasis vulgaris. The biological significance of PUVA therapy for psoriasis vulgaris has mainly been considered to be based on DNA, especially the formation of DNA crosslinks between complementary DNA stands. On the other hand, we have already reported that skin surface lipids were oxidized by UVA irradiation in vitro and this reaction was enhanced in the presence of 8-methoxy-psoralen by a singlet oxygen mechanism. Keeping this in mind, we conducted an experiment to determine whether lipid peroxide can be formed in skin surface lipids following systemic PUVA therapy in psoriasis patients and the following results were obtained: 1) a marked increase of lipid peroxide values in skin surface lipids occurred following PUVA therapy; and 2) the amount of squalene in skin surface lipids was decreased by this treatment. These results indicate that skin surface lipids can be oxidized by PUVA therapy in vivo and this lipid peroxidation on the skin surface may be related to the effects of PUVA therapy on psoriasis vulgaris.

Adult↗
PubMed1980

Lipid dynamics and lipid-protein interactions in rat hepatocyte plasma membranes.

Rat hepatocyte plasma membranes were isolated and examined by differential scanning calorimetry and by steady state fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene, 12-anthroyl stearate, and 2-anthroyl stearate. Calorimetry of the intact membranes revealed a reversible lipid thermotropic transition with lower and upper critical temperatures of 18 degrees and 31 degrees C, respectively. The transition was also observed in lipid extracts of the membrane, both dried and rehydrated. The transition enthalpies estimated for intact membranes, dried membrane lipids, and rehydrated lipids, respectively, were approximately 0.3, 1.2 to 1.4, and 0.5 to 0.7 cal/g of lipid. The transition observed in the native membranes is broad and of low enthalpy, owing in part to the relatively high cholesterol content and to protein-lipid interactions. Fluorescence polarization studies detect the lower critical temperature of the transition in the membranes and in sonicated dispersions of the membrane lipid. Arrhenius studies of membrane 5'-nucleotidase and alkaline phosphatase give two-slope plots with breakpoints, respectively, of approximately 17 degrees and 26 degrees C. These break points and others reported for a number of hepatocyte membrane protein activities cluster uniformly at either the lower or the upper critical temperature of the lipid transition observed by differential scanning calorimetry.

Animals↗
PubMed1997

[Risk factors of arteriopathy of the lower extremities: lipid and not lipid factors].

BACKGROUND: The role of lipoproteins as markers of peripheral arterial disease (PAD) is not well defined. METHODS: We measured both lipid and non-lipid risk factors in 51 male patients with angiographically proven PAD and in 56 control subjects. The independent association of risk factors with PAD was evaluated by means of a multiple logistic regression analysis. RESULTS: The levels of cholesterol bound to high density lipoprotein (HDLc) and to its subfraction HDL2 were lower and triglycerides were higher in patients than in control subjects (1.0 +/- 0.3 vs 1.2 +/- 0.3, p < 0.003; 0.4 +/- 0.2 vs 0.5 +/- 0.3, p < 0.03; and 1.8 +/- 1.2 vs 1.3 +/- 0.7, p < 0.02, respectively). Total cholesterol and LDLc levels were similar in both groups. In the multiple logistic regression analysis that was done with lipid parameters, a statistically significant association of triglycerides (OR = 1.73; CI95% = 1.06-2.80) and HDLc (OR = 0.15; CI95% = 0.05-0.50) with PAD was observed, while HDL subfractions and apolipoproteins were not significantly associated. In the multiple logistic regression analysis that was done with non-lipid parameters, hypertension (OR = 5.35; CI95% = 1.86-15.4) and smoking (packs-year) (OR = 1.04; CI95% = 1.10-1.06) were the only significantly associated with PAD. When lipid and non-lipid parameters were included in the regression analysis, a statistically significant association between hypertension, smoking and HDLc with PAD was observed. CONCLUSIONS: Among lipid risk factors, a low HDLc and high triglycerides, and among non-lipid risk factors hypertension and smoking, are significantly and independently associated with lower limb arteriopathy.

Adult↗
PubMed2005

Multiscale modeling of lipids and lipid bilayers.

A multiscale modeling approach is applied for simulations of lipids and lipid assemblies on mesoscale. First, molecular dynamics simulation of initially disordered system of lipid molecules in water within all-atomic model was carried out. On the next stage, structural data obtained from the molecular dynamics (MD) simulation were used to build a coarse-grained (ten sites) lipid model, with effective interaction potentials computed by the inverse Monte Carlo method. Finally, several simulations of the coarse-grained model on longer length- and time-scale were performed, both within Monte Carlo and molecular dynamics simulations: a periodical sample of lipid molecules ordered in bilayer, a free sheet of such bilayer without periodic boundary conditions, formation of vesicle from a plain membrane, process of self-assembly of lipids randomly dispersed in volume. It was shown that the coarse-grained model, developed exclusively from all-atomic simulation data, reproduces well all the basic features of lipids in water solution.

Computer Simulation↗
PubMed1994

The use of N-(7-nitrobenz-2-oxa-1,3-diazole-4-yl)-labeled lipids in determining transmembrane lipid distribution.

Transbilayer lipid distribution of small unilamellar vesicles (SUVs) and large unilamellar vesicles (LUVs) was measured using 31P-nuclear magnetic resonance (NMR) spectroscopy, chemical modification with 2,4,6-trinitrobenzene sulfonic acid (TNBS) and dithionite reduction of N-(7-nitrobenz-2-oxa-1,3-diazole-4-yl)-labeled lipid (NBD-lipid). The dithionite assay was the most reproducible of the three assays, with 1.2% error for SUVs and 3.9% error for LUVs. The dithionite assay also agreed best with theoretical inner:outer leaflet ratios, based on vesicle diameters determined by electron microscopy (Thomas et al. (1989) Biochem. Biophys. Acta 978, 85-90). Dithionite assay measurements were within 2.7% of theoretical ratios for SUVs and 2.3% for LUVs, while the NMR assay for SUVs was 14% lower than theoretical ratios and 23% lower for LUVs. The accuracy of NBD-lipids as markers for total transbilayer lipid was investigated. NBD-labeled phosphatidylserine, phosphatidylcholine and phosphatidylglycerol were accurate markers for total transbilayer lipid distribution, as their distributions were in close agreement with theoretical ratios. However, NBD-labeled phosphatidylethanolamine displayed a slight preference for the inner leaflet at low mole fractions of phosphatidylethanolamine, while native phosphatidylethanolamine showed a preference for the outer leaflet at the same concentration. NBD-labeled phosphatidic acid also showed a slight preference for the inner leaflet. We conclude that although dithionite-based assessment of NBD-labeled lipids across membrane bilayers can be a powerful analytical tool, caution must be used in the interpretation of results.

4-Chloro-7-nitrobenzofurazan↗
PubMed2001

Lipid-mediated interactions between intrinsic membrane proteins: dependence on protein size and lipid composition.

The present study is an application of an approach recently developed by the authors for describing the structure of the hydrocarbon chains of lipid-bilayer membranes (LBMs) around embedded protein inclusions ( Biophys. J. 79:2867-2879). The approach is based on statistical mechanical integral equation theories developed for the study of dense liquids. First, the configurations extracted from molecular dynamics simulations of pure LBMs are used to extract the lateral density-density response function. Different pure LBMs composed of different lipid molecules were considered: dioleoyl phosphatidylcholine (DOPC), palmitoyl-oleoyl phosphatidylcholine (POPC), dipalmitoyl phosphatidylcholine (DPPC), and dimyristoyl phosphatidylcholine (DMPC). The results for the lateral density-density response function was then used as input in the integral equation theory. Numerical calculations were performed for protein inclusions of three different sizes. For the sake of simplicity, protein inclusions are represented as hard smooth cylinders excluding the lipid hydrocarbon core from a small cylinder of 2.5 A radius, corresponding roughly to one aliphatic chain, a medium cylinder of 5 A radius, corresponding to one alpha-helix, and a larger cylinder of 9 A radius, representing a small protein such as the gramicidin channel. The lipid-mediated interaction between protein inclusions was calculated using a closed-form expression for the configuration-dependent free energy. This interaction was found to be repulsive at intermediate range and attractive at short range for two small cylinders in POPC, DPPC, and DMPC bilayers, whereas it oscillates between attractive and repulsive values in DOPC bilayers. For medium size cylinders, it is again repulsive at intermediate range and attractive at short range, but for every model LBM considered here. In the case of a large cylinder, the lipid-mediated interaction was shown to be repulsive for both short and long ranges for the DOPC, POPC, and DPPC bilayers, whereas it is again repulsive and attractive for DMPC bilayers. The results indicate that the packing of the hydrocarbon chains around protein inclusions in LBMs gives rise to a generic (i.e., nonspecific) lipid-mediated interaction which favors the association of two alpha-helices and depends on the lipid composition of the membrane.

Computer Simulation↗