Cholesterol, mixed monolayers with

Contrary to the case of Q3P, cholesterol only slightly disordered the structure of the film in the mixed monolayers with DPPC or SM. No brightly expressed phase separation was found despite of essential variations (from 60 to 20%) in molar ratio of the alcohol in DPPC/CHL or SM/CHL mixtures. 

In monolayers n-A-isotherms n-A-isotherms of mixed monolayers with cholesterol and distearoylcephalin 98.115-117) 111)... 

Barnes and co-workers have studied mixed-monolayer systems [278,281,283,284] and found some striking nonidealities. Mixed films of octadecanol and cholesterol, for example, show little evaporation resistance if only 10% cholesterol is present [278] apparently due to an uneven granular microstructure in films with cholesterol [284]. Another study of cellulose decanoate films showed no correlation between holes in the monolayer and permeation rate [285]. Polymerized surfactants make relatively poor water evaporation retarders when compared to octadecanol [286]. There are problems in obtaining reproducible values for r [287] due to impurities in the monolayer material or in the spreading solvent. 

The ability of a chiral molecule to distinguish between the enantiomers of a second (different) chiral molecule was defined in Sect. II as a diastereomer discrimination. This phenomenon may be observed in a mixed monolayer of two chiral surfactants and may also occur when a chiral substance is dissolved in the aqueous subphase under the monolayer of a second chiral substance. As before, examples of such chiral discrimination would not include those whose difference in monolayer behavior results only from the gross structural differences of diastereomers such as the different force-area characteristics exhibited by mixed monolayers of l-oleoyl-2-stearoyl-3-s -phospha-tidylcholine with epimeric steroids (120). The relevant experiment, that of comparing the monolayer behavior of mixed monolayers of cholesterol with enantiomeric phospholipids, has been reported (121). As might be anticipated from our previous discussion of... 

The spread mixed lipid monolayer studies provide information about the packing and orientation of such molecules at the water interface. These interfacial characteristics affect many other systems. For instance, mixed surfactants are used in froth flotation. The monolayer surface pressure of a pure surfactant is measured after the injection of the second surfactant. From the change in n, the interaction mechanism can be measured. The monolayer method has also been used as a model biological membrane system. In the latter BLM, lipids are found to be mixed with other lipidlike molecules (such as cholesterol). Hence, mixed monolayers of lipids + cholesterol have been found to provide much useful information on BLM. The most important BLM and temperature melting phenomena is the human body temperature regulation. Normal body temperature is 37°C (98°F), at which all BLM function efficiently. 

The different behavior of 7 and 8 is probably due to the charged head group in 7. Phase separation to form enriched domains of this lipid in mixed monolayers would be inhibited by electrostatic repulsion. Interestingly, mono-layer films of 7 mixed with the biologically important molecule cholesterol did exhibit phase separation at all compositions provided the temperature was maintained below the Tm of 7. Presumably the significantly different shapes of the two molecules promotes the phase separation and overcomes the electrostatic barrier. 

This lamellar phase is formed of alternate sheets of lipid and water. The lipidic sheets containing the lecithin and the cholesterol are made of two superposed layers of oriented molecules. Each of these two monolayers is mixed and consists of lecithin and cholesterol molecules arranged side by side with their paraffinic ends turned toward the inside of the sheet and their polar groups (phosphatidyl choline group for lecithin and hydroxyl group for the cholesterol) outward—i.e., toward the adjacent sheet of water. This constitution of each of the two mono-layers forming the lipidic sheet is in conformity with the conclusion arising from the study of mixed monolayers of cholesterol and lecithin spread on the free surface of water (1). 

With a condensed monolayer, such as cholesterol, it may safely be assumed that each molecule occupies essentially the same area in both pure and mixed films (4). This value is approximately 38 sq. A. per cholesterol molecule. By making this assumption it is possible to obtain, by the method of intercepts (16), the partial molecular areas, (dA/dn)rr,T, at constant r and temperature, of the expanded component in a cholesterol-mixed film. An extrapolation (10) through MN (Type I, Figure 12), or MO if linear (Type II, Figure 12) to the Ai ordinate, yields the area per molecule of the expanded component in the mixed films, where the cholesterol content is either equal to or in excess of the compositions denoted by point N (Type I) or point O (Type II). Such... 

Surface Potential. Shah and Schulman have proposed that interaction between dipoles of uncharged lipids in mixed monolayers should result in a change in surface potential, AV. Linearity of the relation of AV to composition of the lecithin-cholesterol monolayer was taken to indicate absence of interaction (17). We do not agree with Shah and Schulman, since surface potential does not appear to be a valid criterion for assaying interaction between dipoles of uncharged lipids. Except for the speculations of Shah and Schulman (17, 18), there is neither theoretical nor experimental evidence that dipole-dipole interactions have... 

Recently Bourges, Small, and Dervichian (5) reported that a para-crystalline lamellar structure of egg lecithin can solubilize cholesterol up to a maximum of one molecule of cholesterol per molecule of lecithin. However, they conclude that this should not be considered as a molecular association but rather the consequence of the relative arrangement of the molecules in the lamellar structure which is a mutual (solid) solution of lecithin and cholesterol. They also reported that the state of compression in the lamellar structure corresponds to that of a highly compressed mixed monolayer of lecithin-cholesterol. The NMR results of Chapman and Penkett (8) also appear to indicate that solubilization of cholesterol in egg lecithin dispersions results in a highly packed structure in which fatty acyl chains possess little molecular motion. Our results from lecithin-cholesterol monolayers also suggest that these mixed mono-layers are two-dimensional solutions with no specific interaction and that the apparent condensation in some instances is caused by the steric factors of the fatty acyl chains and not by the interaction or association between lecithin and cholesterol. 

Various types of molecular interactions which occur in mixed mono-layers can be distinguished by simultaneous measurements of the surface pressure, potential, and fluidity of monolayers. Limitations of Goodrich s thermodynamic treatment of mixed monolayers are mentioned. Surface properties of cholesterol have been correlated with its function in biomembranes. 

Since cholesterol is an important component of many biological membranes mixtures of polymerizable lipids with this sterol are of great interest. In mixed monolayers of natural lipids with cholesterol a pronounced condensation effect , i.e. a reduction of the mean area per molecule of phospholipid is observed68. This influence of cholesterol on diacetylenic lecithin (18, n = 12), however, is not very significant (Fig. 32). Photopolymerization indicates phase separation in this system. Apparently due to the large hydrophobic interactions between the long hydrocarbon chains of... 

Cholesterol does not form micelles because (1) it is not amphiphilic and (2) its flat, rigid, fused-ring structure gives a solid rather than a liquid, mobile hydrocarbon phase necessary for micellar formation. Cholesterol forms mixed micelles with amphiphilic lipids and will enter monolayers. 

The dependence of the ttv values on the composition of the vapor and condensed states for DML-CHOL, DOL-CHOL, and DOL-DML mixtures is shown in Figure 6. The upper curve is the surface vapor pressure as a function of the mole fraction of the liquid-expanded film the lower curve is for the dependence of irv on the composition of the gaseous phase. Ideal mixing behavior is given by the linear dotted line which joins the 7ry° points for each of the pure compounds. In all cases there was complete miscibility of the components as represented by the continuous function of 7rv with x. In the cholesterol mixtures positive deviations from Raoult s law are observed for the mixture of lecithins, ideal mixing is observed. These results confirm those obtained with lipid mixtures—i.e., cholesterol mixed with liquid-expanded lipid films forms rion-ideal mixtures with positive deviations for mixtures of lipids which are in the same monolayer state, as in the case of the liquid-expanded DOL-DML mixtures, ideal mixing results (8). 

In the small intestine, pancreozymin causes the gallbladder to contract, and bile, a micellar solution of bile acids, lecithin, and cholesterol, is secreted into the duodenum. Pancreozymin also causes discharge and continued synthesis of pancreatic lipase which adsorbs to the oil-water interface, liberating 2-monoglycerides and fatty acids (76). Whether bile acids adsorb to the interface and if so how they spatially orient with respect to lipolytic products and lipase is unknown. At concentrations below the CMC, bile acids will adsorb to monolayers of lipolytic products (77), but no information is available on the interaction of bile acid solutions above their CMC with monolayers of lipolytic products. Somehow, the lipolytic products are transferred to the bulk phase, where they form mixed micelles with bile acid molecules (Fig. 14). 

Using an automated film balance the behavior of mixed monomolecular films exhibiting deviations from ideality was studied. Particular attention was paid to condensation effects obtained when cholesterol is mixed with a more expanded component. The deviations at various film pressures are discussed in terms of the partial molecular areas of the film components. Slope changes in these plots are caused by phase transitions of the expanded monolayer component and do not indicate the formation of surface complexes. In addition, the excess free energies, entropies, and enthalpies of mixing were evaluated, but these parameters could be interpreted only for systems involving pure expanded components, for which it is clear that the observed condensation effects must involve molecular interactions. 

Discontinuities are seen in the relationship between increase in film pressure, An, and lipid composition following the injection of globulin under monolayers of lecithin-dihydro-ceramide lactoside and lecithin-cholesterol mixtures. The breaks occur at 80 mole % C 16-dihydrocaramide lactoside and 50 mole % cholesterol. Between 0 and 80 mole % lactoside and between 0 and 50 mole % cholesterol the mixed films behave as pure lecithin. Two possible explanations are the formation of complexes, having molar ratios of lecithin-lactoside 1 to 4 and lecithin-cholesterol 1 to 1 and/or the effect of monolayer configurations (surface micelles). In this model, lecithin is at the periphery of the surface micelle and shields the other lipid from interaction with globulin. 

Even though 1,2-dilinoleoyl and l-palmitoyl-2-linolenoyl lecithins form more expanded monolayers than egg lecithin, their mixed mono-layers with cholesterol follow the additivity rule (48). This can be explained as follows. At low surface pressures, these lecithins have greater intermolecular spacing and hence form intermolecular cavities of smaller height which cannot accommodate cholesterol molecules (Figure 4e). At high surface pressure, the linoleoyl and linolenoyl chains, as opposed to oleoyl chains, do not form cavities in the monolayer (Figure lOi). 

F. Muller-Landau and D.A. Cadenhead, Molecular packing in steroid-lecithin monolayers, Part II, Mixed films of cholesterol with dipalmitoylphosphatidylcholine, and tetradeanoic acid, Chem. Phys. Lipids 25 (1979) 315-328. 

Thermodynamic parameters for the mixing of dimyristoyl lecithin (DML) and dioleoyl lecithin (DOL) with cholesterol (CHOL) in monolayers at the air-water interface were obtained by using equilibrium surface vapor pressures irv, a method first proposed by Adam and Jessop. Typically, irv was measured where the condensed film is in equilibrium with surface vapor (V < 0.1 0.001 dyne/cm) at 24.5°C this exceeded the transition temperature of gel liquid crystal for both DOL and DML. Surface solutions of DOL-CHOL and DML-CHOL are completely miscible over the entire range of mole fractions at these low surface pressures, but positive deviations from ideal solution behavior were observed. Activity coefficients of the components in the condensed surface solutions were greater than 1. The results indicate that at some elevated surface pressure, phase separation may occur. In studies of equilibrium spreading pressures with saturated aqueous solutions of DML, DOL, and CHOL only the phospholipid is present in the surface film. Thus at intermediate surface pressures, under equilibrium conditions (40 > tt > 0.1 dyne/cm), surface phase separation must occur. 

In addition, it is generally observed for mixtures of aliphatic hydrocarbons that if there is a difference in molecular size, a negative excess volume of mixing results (21). For the lecithin-cholesterol mixtures molecular area decreases (Figure 7), but it does not decrease with the mixture of the lecithins which forms an ideal mixture. Thus, the mixing of cholesterol and lecithin monolayers is consistent with bulk hydrocarbon mixtures with respect to both positive excess heats and negative excess volumes of mixing. 

Especially, for monolayers consisting of more than one substance, there is an immense amonnt of information contained in the pressure-area isotherm. For example, a mixed behenic acid/cholesterol film gives what seems at first sight to be a very noisy isotherm, bnt in fact it contains characteristic oscillation freqnencies, as can readily be seen from the Fourier transform of the derivative (with respect to time the monolayer was compressed at a uniform rate, hence in effect making area and time equivalent) of the isotherm (Figure 5). The origin of these oscillations has been traced to spatial structming. ... 

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