RESUMO
Omega-O-acyl ceramides such as 32-linoleoyloxydotriacontanoyl sphingosine (Cer[EOS]) are essential components of the lipid skin barrier, which protects our body from excessive water loss and the penetration of unwanted substances. These ceramides drive the lipid assembly to epidermal-specific long periodicity phase (LPP), structurally much different than conventional lipid bilayers. Here, we synthesized Cer[EOS] with selectively deuterated segments of the ultralong N-acyl chain or deuterated or 13C-labeled linoleic acid and studied their molecular behavior in a skin lipid model. Solid-state 2H NMR data revealed surprising molecular dynamics for the ultralong N-acyl chain of Cer[EOS] with increased isotropic motion toward the isotropic ester-bound linoleate. The sphingosine moiety of Cer[EOS] is also highly mobile at skin temperature, in stark contrast to the other LPP components, N-lignoceroyl sphingosine acyl, lignoceric acid, and cholesterol, which are predominantly rigid. The dynamics of the linoleic chain is quantitatively described by distributions of correlation times and using dynamic detector analysis. These NMR results along with neutron diffraction data suggest an LPP structure with alternating fluid (sphingosine chain-rich), rigid (acyl chain-rich), isotropic (linoleate-rich), rigid (acyl-chain rich), and fluid layers (sphingosine chain-rich). Such an arrangement of the skin barrier lipids with rigid layers separated with two different dynamic "fillings" i) agrees well with ultrastructural data, ii) satisfies the need for simultaneous rigidity (to ensure low permeability) and fluidity (to ensure elasticity, accommodate enzymes, or antimicrobial peptides), and iii) offers a straightforward way to remodel the lamellar body lipids into the final lipid barrier.
Assuntos
Ácido Linoleico , Simulação de Dinâmica Molecular , Esfingosina/análise , Pele/química , Epiderme , Ceramidas/químicaRESUMO
Amyloid-ß peptide interactions with model lipid membranes have been studied by means of small angle neutron scattering and molecular dynamics simulations. These interactions had been indicated recently as an origin of the membrane structure reorganizations between spherical small unilamellar vesicles and planar bicelle-like structures. In present work, we investigate the influence of charge on the peptide-triggered morphological changes by introducing the anionic lipid DMPS to the underlying DMPC membrane. Changes to the membrane thickness and the overall membrane structure with and without Aß25-35 incorporated have been investigated over a wide range of temperatures. Our results document the previously reported morphological reformations between bicelle-like structures present in gel phase and small unilamellar vesicles present in fluid phase to be independent from the charge existence in the system.
Assuntos
Simulação de Dinâmica Molecular , Lipossomas Unilamelares , Lipossomas Unilamelares/química , Lipídeos/química , Bicamadas Lipídicas/químicaRESUMO
Interactions of the divalent cations Ca2+ and Mg2+ with the zwitterionic lipid bilayers prepared of a fully saturated dipalmitoylphosphatidylcholine (DPPC) or a di-monounsaturated dioleoylphosphatidylcholine (DOPC) were studied by using the neutron scattering methods and molecular dynamics simulations. The effect on the bilayer structural properties confirms the direct interactions in all cases studied. The changes are observed in the bilayer thickness and lateral area. The extent of these structural changes, moreover, suggests various mechanisms of the cation-lipid interactions. First, we have observed a small difference when studying DPPC bilayers in the gel and fluid phases, with somewhat larger effects in the former case. Second, the hydration proved to be a factor in the case of DOPC bilayers, with the larger effects in the case of less hydrated systems. Most importantly, however, there was a qualitative difference between the results of the fully hydrated DOPC bilayers and the others examined. These observations then prompt us to suggest an interaction model that is plausibly governed by the lateral area of lipid, though affected indirectly also by the hydration level. Namely, when the interlipid distance is small enough to allow for the multiple lipid-ion interactions, the lipid-ion-lipid bridges are formed. The bridges impose strong attractions that increase the order of lipid hydrocarbon chains, resulting in the bilayer thickening. In the other case, when the interlipid distance extends beyond a limiting length corresponding to the area per lipid of â¼65 Å2, Mg2+ and Ca2+ continue to interact with the lipid groups by forming the separate ion-lipid pairs. As the interactions proposed affect the lipid membrane structure in the lateral direction, they may prove to play their role in other mechanisms lying within the membrane multicomponent systems and regulating for example the lipid-peptide-ion interactions.
RESUMO
The effect of melatonin and/or cholesterol on the structural properties of a model lipid bilayer prepared from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) has been investigated both experimentally and via molecular dynamics (MD) simulations. Neutron reflectometry experiments performed with single supported membranes revealed changes in lipid bilayer thickness upon the introduction of additional components. While the presence of cholesterol led to an increase in membrane thickness, the opposite effect was observed in the case of melatonin. The results obtained are in a good agreement with MD simulations which provided further information on the organization of components within the systems examined, indicating a mechanism underlying the membranes' thickness changes due to cholesterol and melatonin that had been observed experimentally. Cholesterol and melatonin preferentially accumulate in different membrane regions, presumably affecting the conformation of lipid hydrophobic moieties differently, and in turn having distinct impacts on the structure of the entire membrane. Our findings may be relevant for understanding the effects of age-related changes in cholesterol and melatonin concentrations, including those in the brains of individuals with Alzheimer's disease.
Assuntos
Melatonina , Colesterol , Humanos , Bicamadas Lipídicas , Simulação de Dinâmica Molecular , FosfatidilcolinasRESUMO
The structure and dynamics of membranes depend on many external and internal factors that in turn determine their biological functions. One of the widely accepted and studied characteristics of biomembranes is their fluidity. We research a simple system with variable fluidity tweakable via its composition. The addition of cholesterol is employed to increase the order of lipid chains, thus decreasing the membrane fluidity, while melatonin is shown to elevate the chain disorder, thus also the membrane fluidity. We utilize the densitometric measurements to show a shift of studied systems closer or further from the gel-to-fluid phase transition. The structural changes represented by changes to membrane thickness are evaluated from small angle neutron scattering. Finally, we look at the ability of the two additives to control the interactions between membrane and amyloid-beta peptides. Our results suggest that fluidizing effect of melatonin can promote an insertion of peptide within the membrane interior. Intriguingly, the latter structure relates possibly to an Alzheimer's disease preventing mechanism postulated in the case of melatonin.
Assuntos
Colesterol/química , Melatonina/química , Fluidez de Membrana , Peptídeos beta-Amiloides/química , Bicamadas Lipídicas/química , Conformação Molecular , Fosfatidilcolinas/químicaRESUMO
Membrane models of the stratum corneum (SC) lipid barrier, either healthy or affected by recessive X-linked ichthyosis, constructed from ceramide [Cer; nonhydroxyacyl sphingosine N-tetracosanoyl-d-erythro-sphingosine (CerNS24) alone or with omega-O-acylceramide N-(32-linoleyloxy)dotriacontanoyl-d-erythro-sphingosine (CerEOS)], FFAs(C16-24), cholesterol (Chol), and sodium cholesteryl sulfate (CholS) were investigated. X-ray diffraction (XRD) revealed a previously unreported polymorphism of the membranes. In the absence of CerEOS, the membranes formed a short lamellar phase (SLP; the repeat distance d = 5.3 nm), a medium lamellar phase (MLP; d = 10.6 nm), or very long lamellar phases (VLLP; d = 15.9 and 21.2 nm). An increased CholS-to-Chol ratio modulated the membrane polymorphism, although the CholS phase separated at ≥ 7 weight% (of total lipids). The presence of CerEOS led to the stable long lamellar phase (LLP) with d = 12.2 nm and prevented VLLP formation. Our XRD results agree well with recently published cryo-electron microscopy data for vitreous skin sections, while also revealing new structures. Thus, lamellar phases with long repeat distances (MLP and VLLP) may be formed in the absence of omega-O-acylceramide, whereas these ultralong Cer species likely stabilize the final SC lipid architecture of LLP by riveting the adjacent lipid layers.
Assuntos
Ictiose Ligada ao Cromossomo X/metabolismo , Lipídeos de Membrana/metabolismo , Modelos Biológicos , Pele/química , Microscopia Crioeletrônica , Humanos , Ictiose Ligada ao Cromossomo X/genética , Ictiose Ligada ao Cromossomo X/patologia , Lipídeos de Membrana/química , Pele/metabolismo , Pele/patologiaRESUMO
Interactions of calcium (Ca2+) and zinc (Zn2+) cations with biomimetic membranes made of dipalmitoylphosphatidylcholine (DPPC) were studied by small angle neutron diffraction (SAND). Experiments show that the structure of these lipid bilayers is differentially affected by the two divalent cations. Initially, both Ca2+ and Zn2+ cause DPPC bilayers to thicken, while further increases in Ca2+ concentration result in the bilayer thinning, eventually reverting to having the same thickness as pure DPPC. The binding of Zn2+, on the other hand, causes the bilayers to swell to a maximum thickness, and the addition of more Zn2+ does not result in a further thickening of the membrane. Agreement between our results obtained using oriented planar membranes and those from vesicular samples implies that the effect of cations on bilayer thickness is the result of electrostatic interactions, rather than geometrical constraints due to bilayer curvature. This notion is further reinforced by MD simulations. Finally, the radial distribution functions reveal a strong interaction between Ca2+ and the phosphate oxygens, while Zn2+ shows a much weaker binding specificity.
Assuntos
1,2-Dipalmitoilfosfatidilcolina/química , Cálcio/química , Bicamadas Lipídicas/química , Zinco/química , Materiais Biomiméticos/química , Simulação de Dinâmica MolecularRESUMO
We investigate the structural changes to lipid membrane that ensue from the addition of aliphatic alcohols with various alkyl tail lengths. Small angle neutron diffraction from flat lipid bilayers that are hydrated through water vapor has been employed to eliminate possible artefacts of the membrane curvature and the alcohol's membrane-water partitioning. We have observed clear changes to membrane structure in both transversal and lateral directions. Most importantly, our results suggest the alteration of the membrane-water interface. The water encroachment has shifted in the way that alcohol loaded bilayers absorbed more water molecules when compared to the neat lipid bilayers. The experimental results have been corroborated by molecular dynamics simulations to reveal further details. Namely, the order parameter profiles have been fruitful in correlating the mechanical model of structural changes to the effect of anesthesia.
Assuntos
Álcoois/química , Bicamadas Lipídicas/química , Algoritmos , Lipídeos/química , Modelos Químicos , Conformação Molecular , Simulação de Dinâmica MolecularRESUMO
Aspirin and other non-steroidal anti-inflammatory drugs have a high affinity for phospholipid membranes, altering their structure and biophysical properties. Aspirin has been shown to partition into the lipid head groups, thereby increasing membrane fluidity. Cholesterol is another well known mediator of membrane fluidity, in turn increasing membrane stiffness. As well, cholesterol is believed to distribute unevenly within lipid membranes leading to the formation of lipid rafts or plaques. In many studies, aspirin has increased positive outcomes for patients with high cholesterol. We are interested if these effects may be, at least partially, the result of a non-specific interaction between aspirin and cholesterol in lipid membranes. We have studied the effect of aspirin on the organization of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) membranes containing cholesterol. Through Langmuir-Blodgett experiments we show that aspirin increases the area per lipid and decreases compressibility at 32.5 mol% cholesterol, leading to a significant increase of fluidity of the membranes. Differential scanning calorimetry provides evidence for the formation of meta-stable structures in the presence of aspirin. The molecular organization of lipids, cholesterol and aspirin was studied using neutron diffraction. While the formation of rafts has been reported in binary DPPC/cholesterol membranes, aspirin was found to locally disrupt membrane organization and lead to the frustration of raft formation. Our results suggest that aspirin is able to directly oppose the formation of cholesterol structures through non-specific interactions with lipid membranes.
Assuntos
Aspirina/química , Colesterol/química , Bicamadas Lipídicas/química , Lipídeos de Membrana/química , Microdomínios da Membrana/química , 1,2-Dipalmitoilfosfatidilcolina/química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Varredura Diferencial de Calorimetria , Membrana Celular/química , Membrana Celular/efeitos dos fármacos , Humanos , Cinética , Fluidez de Membrana , Modelos Químicos , Modelos Moleculares , Estrutura Molecular , Difração de NêutronsRESUMO
The presumptive function for alpha-tocopherol (αtoc) in membranes is to protect polyunsaturated lipids against oxidation. Although the chemistry of the process is well established, the role played by molecular structure that we address here with atomistic molecular-dynamics simulations remains controversial. The simulations were run in the constant particle NPT ensemble on hydrated lipid bilayers composed of SDPC (1-stearoyl-2-docosahexaenoylphosphatidylcholine, 18:0-22:6PC) and SOPC (1-stearoyl-2-oleoylphosphatidylcholine, 18:0-18:1PC) in the presence of 20 mol % αtoc at 37°C. SDPC with SA (stearic acid) for the sn-1 chain and DHA (docosahexaenoic acid) for the sn-2 chain is representative of polyunsaturated phospholipids, while SOPC with OA (oleic acid) substituted for the sn-2 chain serves as a monounsaturated control. Solid-state (2)H nuclear magnetic resonance and neutron diffraction experiments provide validation. The simulations demonstrate that high disorder enhances the probability that DHA chains at the sn-2 position in SDPC rise up to the bilayer surface, whereby they encounter the chromanol group on αtoc molecules. This behavior is reflected in the van der Waals energy of interaction between αtoc and acyl chains, and illustrated by density maps of distribution for acyl chains around αtoc molecules that were constructed. An ability to more easily penetrate deep into the bilayer is another attribute conferred upon the chromanol group in αtoc by the high disorder possessed by DHA. By examining the trajectory of single molecules, we found that αtoc flip-flops across the SDPC bilayer on a submicrosecond timescale that is an order-of-magnitude greater than in SOPC. Our results reveal mechanisms by which the sacrificial hydroxyl group on the chromanol group can trap lipid peroxyl radicals within the interior and near the surface of a polyunsaturated membrane. At the same time, water-soluble reducing agents that regenerate αtoc can access the chromanol group when it locates at the surface.
Assuntos
Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Oxirredução , Fosfolipídeos/química , alfa-Tocoferol/química , Peroxidação de Lipídeos , Espectroscopia de Ressonância Magnética , Difração de NêutronsRESUMO
We recently published two papers detailing the structures of fluid phase phosphatidylglycerol (PG) lipid bilayers (Kucerka et al., 2012 J. Phys. Chem. B 116: 232-239; Pan et al., 2012 Biochim. Biophys. Acta Biomembr. 1818: 2135-2148), which were determined using the scattering density profile model. This hybrid experimental/computational technique utilizes molecular dynamics simulations to parse a lipid bilayer into components whose volume probabilities follow simple analytical functional forms. Given the appropriate scattering densities, these volume probabilities are then translated into neutron scattering length density (NSLD) and electron density (ED) profiles, which are used to jointly refine experimentally obtained small angle neutron and X-ray scattering data. However, accurate NSLD and ED profiles can only be obtained if the bilayer's chemical composition is known. Specifically, in the case of neutron scattering, the lipid's exchangeable hydrogens with aqueous D2O must be accounted for, as they can have a measureable effect on the resultant lipid bilayer structures. This was not done in our above-mentioned papers. Here we report on the molecular structures of PG lipid bilayers by appropriately taking into account the exchangeable hydrogens. Analysis indicates that the temperature-averaged PG lipid areas decrease by 1.5 to 3.8Å(2), depending on the lipid's acyl chain length and unsaturation, compared to PG areas when hydrogen exchange was not taken into account.
RESUMO
To this day, α-tocopherol's (aToc) role in humans is not well known. In previous studies, we have tried to connect aToc's biological function with its location in a lipid bilayer. In the present study, we have determined, by means of small-angle neutron diffraction, that not only is aToc's hydroxyl group located high in the membrane but its tail also resides far from the center of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. In addition, we located aToc's hydroxyl group above the lipid backbone in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS), and sphingomyelin bilayers, suggesting that aToc's location near the lipid-water interface may be a universal property of vitamin E. In light of these data, how aToc efficiently terminates lipid hydroperoxy radicals at the membrane center remains an open question.
Assuntos
Bicamadas Lipídicas/química , Água/química , alfa-Tocoferol/química , Humanos , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Fosfatidilserinas/química , Esfingomielinas/química , Propriedades de Superfície , Temperatura , TermodinâmicaRESUMO
Specular neutron reflectometry was measured on a floating bilayer system consisting of 1,2-dipalmitoyl-d62-sn-glycero-3-phosphocholine deposited over a 1,2-dibehenoyl-sn-glycero-3-phosphocholine bilayer at 25 and 55 °C. The internal structure of lipid bilayers was described by a one-dimensional neutron scattering length density profile model, originally developed for the evaluation of small-angle scattering data. The reflectivity data from the supported bilayer were evaluated separately and used further as constraints in modeling the floating bilayer reflectivity curves. The model reflectivity curves successfully describe the experimental reflectivities of the supported bilayer in the gel phase and the floating bilayer system in the liquid-crystalline phase. The results yield an internal structure of a deposited bilayer and a floating bilayer on the level of component groups of lipid molecules. The obtained structure of the floating d62-diC16:0PC bilayer displays high resemblance of the bilayer structure in the form of unilamellar vesicles. At the same time, however, the results show differences in comparison to unilamellar vesicle bilayers, most likely due to the undulations of supported bilayers.
Assuntos
Dimiristoilfosfatidilcolina/química , Bicamadas Lipídicas/química , Fosfatidilcolinas/química , Lipossomas Unilamelares/química , Difração de Nêutrons , Espalhamento a Baixo ÂnguloRESUMO
Mixtures of dimyristoyl-phosphatidylcholine (DMPC), dimyristoyl-phosphatidylglycerol (DMPG) and dihexanoyl-phosphatidylcholine (DHPC) in aqueous solutions spontaneously form monodisperse, bilayered nanodiscs (also known as "bicelles") at or below the melting transition temperature of DMPC (T(M) ~23°C). In dilute systems above the main transition temperature T(M) of DMPC, bicelles coalesce (increasing their diameter) and eventually self-fold into unilamellar vesicles (ULVs). Time-resolved small angle neutron scattering was used to study the growth kinetics of nanodiscs below and equal to T(M) over a period of hours as a function of temperature at two lipid concentrations in presence or absence of NaCl salt. Bicelles seem to undergo a sudden initial growth phase with increased temperature, which is then followed by a slower reaction-limited growth phase that depends on ionic strength, lipid concentration and temperature. The bicelle interaction energy was derived from the colloidal theory of Derjaguin and Landau, and Verwey and Overbeek (DLVO). While the calculated total energy between discs is attractive and proportional to their growth rate, a more detailed mechanism is proposed to describe the mechanism of disc coalescence. After annealing at low temperature (low-T), samples were heated to 50°C in order to promote the formation of ULVs. Although the low-T annealing of samples has only a marginal effect on the mean size of end-state ULVs, it does affect their polydispersity, which increases with increased T, presumably driven by the entropy of the system.
Assuntos
Lipossomas Unilamelares/química , Biofísica/métodos , Dimiristoilfosfatidilcolina/química , Cinética , Bicamadas Lipídicas/química , Nanopartículas/química , Nanotecnologia/métodos , Nêutrons , Fosfatidilgliceróis/química , Éteres Fosfolipídicos/química , Espalhamento de Radiação , Espalhamento a Baixo Ângulo , Temperatura , Fatores de TempoRESUMO
Using data obtained from different physical techniques (i.e., neutron diffraction, NMR and UV spectroscopy), we present evidence which explains some of the conflicting and inexplicable data found in the literature regarding α-tocopherol's (aToc's) behavior in dimyristoyl phosphatidylcholine (di-14:0PC) bilayers. Without exception, the data point to aToc's active chromanol moiety residing deep in the hydrophobic core of di-14:0PC bilayers, a location that is in stark contrast to aToc's location in other PC bilayers. Our result is a clear example of the importance of lipid species diversity in biological membranes and importantly, it suggests that measurements of aToc's oxidation kinetics, and its associated byproducts observed in di-14:0PC bilayers, should be reexamined, this time taking into account its noncanonical location in this bilayer.
Assuntos
Dimiristoilfosfatidilcolina/química , Bicamadas Lipídicas/química , alfa-Tocoferol/química , Lipossomos/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Difração de NêutronsRESUMO
Rafts, or functional domains, are transient nano-or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking, and lipid or protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules, we observe raftlike structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to ordering of the cholesterol molecules in the raftlike structures were observed and indexed by two different structures: a monoclinic structure of ordered cholesterol pairs of alternating direction in equilibrium with cholesterol plaques, i.e., triclinic cholesterol bilayers.
RESUMO
Small-angle neutron scattering data were collected from aqueous dispersions of unilamellar vesicles (ULVs) consisting of mixtures of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine and a homologous series of N,N-dimethyl-N-alkylamine-N-oxides (CnNO, n = 12, 14, 16, and 18, where n is the number of carbon atoms in the alkyl chain). A modeling approach was applied to the neutron scattering curves to obtain the bilayer structural parameters. Particularly, the external (2)H2O/H2O contrast variation technique was carried out on pure dioleoylphosphatidylcholine (DOPC) ULVs to determine the hydrophilic region thickness [Formula: see text] = 9.8 ± 0.6 Å. Consequently, the hydrocarbon region thickness [Formula: see text], the lateral bilayer area per one lipid molecule [Formula: see text], and the number of water molecules located in the hydrophilic region per one lipid molecule [Formula: see text] were obtained from single-contrast neutron scattering curves using the previously determined [Formula: see text]. The structural parameters were extracted as functions of [Formula: see text] (the CnNO:DOPC molar ratio) and n. The dependences [Formula: see text] provided the partial lateral areas of CnNOs ([Formula: see text]) and DOPC ([Formula: see text]) in bilayers. It was observed that the [Formula: see text]'s were constant in the investigated interval of [Formula: see text] and for n = 12, 14, and 16 equal to 36.6 ± 0.4 Å(2), while [Formula: see text] increased to 39.4 ± 0.4 Å(2). The bilayer hydrocarbon region thickness [Formula: see text] decreased with intercalation of each CnNO. This effect increased with [Formula: see text] and decreased with increasing CnNO alkyl chain length. The intercalation of C18NO changed the [Formula: see text] only slightly. To quantify the effect of CnNO intercalation into DOPC bilayers we fit the [Formula: see text] dependences with weighted linear approximations and acquired their slopes [Formula: see text].
Assuntos
Dimetilaminas/farmacologia , Bicamadas Lipídicas/química , Difração de Nêutrons , Fosfatidilcolinas , Espalhamento a Baixo Ângulo , Lipossomas Unilamelares/química , Relação Dose-Resposta a DrogaRESUMO
Phosphatidylserine (PS) lipids play essential roles in biological processes, including enzyme activation and apoptosis. We report on the molecular structure and atomic scale interactions of a fluid bilayer composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine (POPS). A scattering density profile model, aided by molecular dynamics (MD) simulations, was developed to jointly refine different contrast small-angle neutron and X-ray scattering data, which yielded a lipid area of 62.7 Å(2) at 25 °C. MD simulations with POPS lipid area constrained at different values were also performed using all-atom and aliphatic united-atom models. The optimal simulated bilayer was obtained using a model-free comparison approach. Examination of the simulated bilayer, which agrees best with the experimental scattering data, reveals a preferential interaction between Na(+) ions and the terminal serine and phosphate moieties. Long-range inter-lipid interactions were identified, primarily between the positively charged ammonium, and the negatively charged carboxylic and phosphate oxygens. The area compressibility modulus KA of the POPS bilayer was derived by quantifying lipid area as a function of surface tension from area-constrained MD simulations. It was found that POPS bilayers possess a much larger KA than that of neutral phosphatidylcholine lipid bilayers. We propose that the unique molecular features of POPS bilayers may play an important role in certain physiological functions.
Assuntos
Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Fosfatidilserinas/química , Óxido de Deutério/química , Íons/química , Difração de Nêutrons , Espalhamento a Baixo Ângulo , Sódio/química , Água/química , Difração de Raios XRESUMO
We have studied the effect of calcium ions (Ca2+) at various concentrations on the structure of lipid vesicles in the presence of amyloid-beta peptide Aß(25-35). In particular, we have investigated the influence of calcium ions on the formation of recently documented bicelle-like structures (BLSs) emerged as a result of Aß(25-35) triggered membrane disintegration. First, we have shown by using small-angle X-ray and neutron scattering that peptide molecules rigidify the lipid bilayer of gel phase DPPC unilamellar vesicles (ULVs), while addition of the calcium ions to the system hinders this effect of Aß(25-35). Secondly, the Aß(25-35) demonstrates a critical peptide concentration at which the BLSs reorganize from ULVs due to heating and cooling the samples through the lipid main phase transition temperature (Tm). However, addition of calcium ions does not affect noticeably the Aß-induced formation of BLSs and their structural parameters, though the changes in peptide's secondary structure, e.g. the increased α-helix fraction, has been registered by circular dichroism spectroscopy. Finally, according to 31P nuclear magnetic resonance (NMR) measurements, calcium ions do not affect the lipid-peptide arrangement in BLSs and their ability to align in the magnetic field of NMR spectrometer. The influences of various concentrations of calcium ions on the lipid-peptide interactions may prove biologically important because their local concentrations vary widely in in-vivo conditions. In the present work, calcium ions were investigated as a possible tool aimed at regulating the lipid-peptide interactions that demonstrated the disruptive effect of Aß(25-35) on lipid membranes.
RESUMO
Tools based on artificial intelligence (AI) are currently revolutionising many fields, yet their applications are often limited by the lack of suitable training data in programmatically accessible format. Here we propose an effective solution to make data scattered in various locations and formats accessible for data-driven and machine learning applications using the overlay databank format. To demonstrate the practical relevance of such approach, we present the NMRlipids Databank-a community-driven, open-for-all database featuring programmatic access to quality-evaluated atom-resolution molecular dynamics simulations of cellular membranes. Cellular membrane lipid composition is implicated in diseases and controls major biological functions, but membranes are difficult to study experimentally due to their intrinsic disorder and complex phase behaviour. While MD simulations have been useful in understanding membrane systems, they require significant computational resources and often suffer from inaccuracies in model parameters. Here, we demonstrate how programmable interface for flexible implementation of data-driven and machine learning applications, and rapid access to simulation data through a graphical user interface, unlock possibilities beyond current MD simulation and experimental studies to understand cellular membranes. The proposed overlay databank concept can be further applied to other biomolecules, as well as in other fields where similar barriers hinder the AI revolution.