Membrane systems lipid model

Ion Binding and Water Orientation in Lipid Model Membrane Systems Studied by NMR... 

In order to elucidate the physicochemical properties of such a biological membrane interface, several model membrane systems (lipid monolayer, lipid bilayers, and protein-incorporated lipid model membrane systems) which mimic biological membrane interfaces have also been studied.In particular, many properties at the membrane surface are intimately related to the electrical potential originating from the fixed charge or electrical polarization of the membrane constitutents. 

Figure 2. Model membrane systems, (a) Monolayer at the gas-water interface, (b) Planar bimolecular lipid membrane (BLM). (c) Liposomes.

The polymerization of the butadiene monomers (3,4) can also be followed spectroscopically by the disappearance of the strong absorption of the monomers at 260 nm, whereas the absorption of the resulting poly-1,4-trans(butadiene)s is too small to be observed in a single monolayer. The polymers from the butadiene and methacryloyl lipids are probably better model membrane systems, because the polymer chains are still mobile and not excessively rigid as the polydiacetylenes. 

L. Davenport, R. E. Dale, R. H. Bisby, and R. B. Cundall, Transverse location of the fluorescent probe l,6-diphenyl-l,3,5-hexatriene in model lipid bilayer membrane systems by resonance excitation energy transfer, Biochemistry 24, 4097-4108 (1985). 

MD simulations of model membrane systems have provided a unique view of lipid interactions at a molecular level of resolution [21], Due to the inherent fluidity and heterogeneity in lipid membranes, computer simulation is an attractive tool. MD simulations allow us to obtain structural, dynamic, and energetic information about model lipid membranes. Comparing calculated structural properties from our simulations to experimental values, such as areas and volumes per lipid, and electron density profiles, allows validation of our models. With molecular resolution, we are able to probe lipid-lipid interactions at a level difficult to achieve experimentally. 

Whether polymerized model membrane systems are too rigid for showing a phase transition strongly depends on the type of polymerizable lipid used for the preparation of the membrane. Especially in the case of diacetylenic lipids a loss of phase transi tion can be expected due to the formation of the rigid fully conjugated polymer backbone 20) (Scheme 1). This assumption is confirmed by DSC measurements with the diacetylenic sulfolipid (22). Figure 25 illustrates the phase transition behavior of (22) as a function of the polymerization time. The pure monomeric liposomes show a transition temperature of 53 °C, where they turn from the gel state into the liquid-crystalline state 24). During polymerization a decrease in phase transition enthalpy indicates a restricted mobility of the polymerized hydrocarbon core. Moreover, the phase transition eventually disappears after complete polymerization of the monomer 24). 

Hope, M. J., Wong, K. F., and Cullis, P. R. (1989), Freeze-fracture of lipids and model membrane systems, J. Electron. Microsc. Tech., 13,277-287. 

McElhaney, R. N. Differential scanning calorimetric studies of lipid-protein interactions in model membrane systems. Biochimica et Biophysica acta 564 361-421, 1986. 

The preliminary results just reported for DPPC/OA monolayers illustrate the way in which neutron reflectometry can be used to study the interaction of components in model membrane systems. In particular, the technique has been shown to be useful in the study of the water associated with lipid headgroups. Data analysis by the partial stmcture factor method offers the potential to study complex multicomponent membrane systems, which have more relevance to the behavior of biological membranes in vivo. 

Mention should be made here of the recently developed technique of pressure perturbation calorimetry (PPC), which measures the temperature-dependent volume change of a solute or colloidal particle in aqueous solution. PPC can also be used to detect thermotropic phase transitions in lipid model membranes and to characterize the accompanying volume changes and the kinetics of the phase transition. PPC essentially measures the heat change that results from small pressure changes at a constant temperature in a high-sensitivity isothermal calorimeter. For an excellent recent review on PPC as applied to lipid systems, the reader is referred to Heerklotz (19). 

Trauble H, Sackmann E. Studies of crystalline-liquid crystalline phase-transihon of lipid model membranes.3. Structure of a steroid-lecithin system below and above lipid-phase transition. J. Am. Chem. Soc. 1972 94 4499-4510. 

Tamm LK. The substrate supported lipid bilayer-a new model membrane system. Klin. Wochenschr. 1984 62 502-503. 

Single- and double-chained lipid derivatives of purines and purine nucleosides, such as 1-7, have been prepared. Ultrasonication of such compounds leads to either nucellar (single-chain compounds) or liposomal aggregates (double-chained compounds). Their surface behavior in monolayer, bilayer, and multilayer model membrane systems has been studied. 

The interaction of CNTs with membrane bilayers has been studied mainly with model membrane systems, and limited data have been obtained in vivo. Available evidence indicates that at low pH TeTx and BoNTs undergo a conformational change from a water soluble "neutral" form to an "acidic" form, the latter characterized by the exposure of hydrophobic segments. This increase in hydrophobicity allows penetration of both the H and L chains into the hydrocarbon core of the lipid bilayer (Montecucco etal., 1994). Following this low pH-induced membrane insertion, TeTx and BoNTs form ion channels in planar lipid bilayers (Beise et al., 1994 Montecucco et al., 1994). These channels are cation-selective, have few tens of pS conductance and are per-... 

Many questions pertaining to membrane processes in general and ligand/membrane receptor interactions in particular can be addressed by a novel model membrane system, i.e., polymer-supported or polymer-tethered lipid bilayers [12,14], The basic structural unit for this sensor platform is the tethered lipid bilayer membrane [16] displayed in Fig. 2D. The essential architectural elements of this supramolecular assembly include the solid support, e.g., an optical or electrical transducer (device), the polymeric tether system which provides the partial covalent and, hence, very stable attachment of the whole membrane to the substrate surface, and the fluid lipid bilayer, functionalized if needed by embedded proteins. 

Paramagnetic analogs of phospholipids have also been used to investigate lipid transport phenomena in model membrane systems (R.D. Komberg, 1971) and in biological membranes. Representative structures are shown in Fig. 2. Several of these spin-labeled lipid analogs that are modified in the fatty acid chain can be readily and reversibly transferred... 

Both aqueous organic solvent mixtures and differently charged micelles can mimic only roughly the environment of natural cell membranes. In order to analyze in more appropriate model systems possible interactions of gastrin and CCK with cell membranes and to determine their conformational states in lipid bilayers, we have recently investigated in detailed manner this aspect using liposomes. The similarity betwen liposomes and natural membranes is extensively exploited both in vitro and in vivo because of the ability of liposomes to mimic the behaviour of natural membranes. Moreover, the value of liposomes as model membrane systems derives from the fact that they can be constructed with natural constituents. In our approach, we selected as model membranes those formed with the zwitterionic lipids di-myristoylphosphatidylcholine (DMPC) and di-palmitoylphosphatidylcholine (DPPC) as these lipids constitute the major components of most cell membranes. Moreover, in order to operate with a simple system, small unilamellar vesicles (SUVs) were used, i.e. with a diameter between 25 and 250 nm as resulting by rod-type sonication or by extrusion (51). 

A model membrane system that also shows reproducible and clear 1/f behavior was described by Bezrukov and Brutyan (76). Fluctuations of current through lipid bilayers with one-sided application of three different polyene antibiotics of very close chemical structure (i.e., amphotericin B, nystatin, and mycoheptin) were studied. For one-sided application these antibiotics form channels that are weakly bound to the membrane as compared with the channels of the two-sided action. All three compounds produced pronounced noise component with spectral distribution of 1/f type (Figure 8). It was found that the noise intensity scales as the ratio of single channel conductances for amphotericin B, nystatin, and mycoheptin namely, hA hN hM = 10 5 1. For mycoheptin the spectrum is described by the function 1/f0-86 over the whole frequency range used. With two-sided application of these antibiotics, channels are more stable and strongly bound to the bilayer. In this case, significantly lower noise intensities were found the spectrum for amphotericin B was described by a single Lorentzian spectrum of relatively small amplitude (63). 

In multicomponent systems difficulties arise from the overlapping of C-H features due to chemically different lipids, or in hpid-protein arrays, from protein C-H stretching bands. In these systems it becomes impossible to monitor a single lipid component. Mendelsohn et al. [64] showed how this problem csai be overcome by the use of deuterated components. They inserted a completely deuterated fatty acid into a model membrane system and followed the C-D stretching vibrations in the spectral window 2000-2220 cm which is uncluttered by modes from other components. As the membrane passed through a gel-liquid crystal transition the line-width of the C-D stretching vibrations of the bound fatty add was found to be a sensitive probe of membrane polymethylene chain order. 

In order to elucidate adhesion phenomena occurring among biological cells, a number of studies on membrane adhesion using model membrane systems (such as lipid membranes as well as lipid membranes with incorporated proteins) have recently been carried out. Some of these aggregation phenomena have been analyzed from the viewpoint of the DLVO theory 2 " -" ... 

Biological applications of solid state NMR in the area of model membrane systems have been reviewed by Drechsler and Separovic. The advantages of solid state NMR in providing information about how the peptides or proteins interact with the lipids or other peptides/proteins in the membrane, as well as their effect on the membrane and the location of the peptides or proteins relative to the membrane surface are presented. The importance of both recent technique developments and improvements in sample labelling has been emphasised. This review also discusses aligned systems and MAS techniques, bilayers and bicelles, and measurement of chemical shift anisotropy and dipolar coupling. A number of specific experiments such as CP, rotational resonance, REDOR, PISEMA and multidimensional experiments are described. In addition to traditional H, and N studies, recent solid-sate H, 0 and F NMR applications are also included in this review. Finally, several examples of the use of solid state NMR to determine the structure of membrane peptides and proteins are given. 

A good experimental model for biomembranes should possess a lipid bilayer structure, onto as well as into which functional entities can be embedded. Thus, since the 1960s, the two most widely used model membranes have been BLMs, also referred to as planar lipid bilayers and spherical liposomes. Planar BLMs and spherical liposomes are complementary to each other, since both types are derived from common amphipathic lipids and related compounds. Both are excellent model membrane systems, and have been extensively employed for investigations into a variety of physical, chemical, and biological functions. In the remainder of this chapter on membrane electrochemistry, the focus will be mainly on planar BLMs, because they are easily and have been investigated electrochemically (for K-posomes, see Refs. [3, 12, 34]). As a result... 

Early examples of synthetic flippases were lipidated polymers, which used bilayer distortion to bring about lipid flip-flop. In contrast to these mechanical flippases, synthetic species that apply the principles of molecular recognition to create phospholipid complexes capable of transverse diffusion have been shown to enhance lipid flip-flop in model membrane systems. Boon and Smith generated asymmetric bilayers by adding synthetic NBD phospholipids to the outer leaflet of POPC vesicles and then determined the rate of flip-flop to the inner leaflet... 

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