Lecithin-cholate micelles

Fig. 49. Diagrammatic representation of the lecithin-sodium cholate micelle. On the left are represented small micelles containing a larger proportion of bile salt to lecithin. Above are longitudinal sections and below are cross sections of these micelles. On the right are shown larger micelles which have less bile salt and more phospholipid. The micelles are disc-shaped bimolecular leaflets of lecithin surrounded on their hydrophobic parts by a perimeter of bile salt molecules. Wavy lines or hollow circles, alkyl chains of lecithin S, phosphoryl choline of lecithin (67).

The aggregation behavior of C21-DA salt in dilute electrolyte medium appears to resemble that of certain polyhydroxy bile salts (25,16). That C21-DA, with a structure quite different from bile acids, should possess solution properties similar to, e.g., cholic acid is not entirely surprising in light of recent conductivity and surface tension measurements on purified (i.e., essentially monocarboxylate free) disodium salt aqueous solutions, and of film balance studies on acidic substrates (IX) The data in Figure 3 suggest that C21-DA salt micelles Incorporate detergents - up to an approximate weight fraction of 0.5 -much like cholate Incorporates lecithin or soluble... 

Different factors govern the formation of these molecular compounds. Where lipids and related substances are concerned the governing factor is the realization of the best hydrophilic-lipophilic balance producing hydration or dispersion. The case of lecithin and sodium cholate associated in the presence of water may be used to illustrate the conditions of association and formation of different types of structure and of micelles. 

Sodium cholate is insoluble in chloroform and in nonpolar solvents in general, but it is very soluble in alcohol and in water. Lecithin, on the contrary, is soluble in chloroform and only swells in water without dissolving in it. These differences in solubility are evidently related to the molecular structure and to the position of the hydrophilic groups in each of these molecules. The lecithin molecule has two important paraffinic chains and a group of hydrophilic functions (choline phosphate) localized at one end. In the presence of water, the lecithin molecules are oriented with their hydrophilic groups toward the water, and they hide their paraffinic chains inside a structure formed of two superposed layers of molecules. Conversely, in a nonpolar solvent the paraffinic chains are turned toward the solvent, while the polar groups are hidden inside the micelle. 

Figure 2. Schematic view of proposed model for association of lecithin and Na cholate into mixed micelles...

For still larger quantities of water, one obtains the isotropic phase (IV), formed of mixed micelles. By extending the frontier line, WN, up to its intersection with side L-NaC of the triangle of the Figure 3, it can be seen that in order to get this micellar dispersion, at least one molecule of Na cholate is needed for two molecules of lecithin. 

Consider first the weight proportion of 77% of Na cholate for 33% lecithin which has to be reached in order to solubilize all the lecithin in water. This corresponds nearly to one molecule of Na cholate for two of lecithin. Taking as a model the one proposed in Figure 2, we can calculate the size which the mixed micelles should have so that the proportion of one molecule of Na cholate for two of lecithin will be obeyed. In other words, we want to know the number of lecithin molecules packed side by side which, surrounded by a ring of adjacent Na cholate molecules, can give the desired proportion. The calculation gives for each... 

For the proportion of one molecule of Na cholate to one of lecithin —i.e.y 37% Na cholate and 63% lecithin—the same calculation gives 24 molecules of lecithin for 24 of Na cholate in each layer—i.e., 48 molecules of each species for the whole of the mixed micelles and a molecular weight of about 60,000. Finally, for the weight proportion of 1 to 1 (about five molecules of Na cholate for three of lecithin), we find per layer 10 molecules of lecithin for 17 of Na cholate. This leads to 20 molecules of lecithin for 34 of Na cholate for the whole mixed micelle and a molecular weight of about 30,000. 

It is also reasonable to admit that the size of the mixed micelle could be the same in all systems situated along line OW since in all these cases the mixed micelles would always be in equilibrium with a micellar solution of pure Na cholate. Indeed, the chemical potential of the Na cholate in solution remains practically constant whatever the concentration, as long as micelles are present. Consequently, the chemical potential of the Na cholate attached to lecithin on the mixed micelles must also be constant since there is equilibrium. 

These statements lead to the conclusion that the limiting proportion of 1 gram of Na cholate associated to 1 gram of lecithin is simply imposed by the size of a certain form of mixed micelle which can remain in equilibrium with an excess of Na cholate in micellar solution. Thus, it clearly appears that association is governed by the necessity of securing the proper hydrophilic-lipophilic balance of the mixture of two components. Here, as in the case of other amphiphilic substances, by the progressive increase in proportion of the more hydrophilic amphiphile. the association can reach complete micellar dispersion in water. 

For mixtures of lecithin plus Na cholate it appears possible to infer the molecular arrangement in the dispersed micelles from the most likely structure of the liquid crystalline phase suggested by x-ray analysis. However, there are cases where dispersion is not possible because neither component is sufficiently hydrophilic to be dispersed even when alone in water. This is shown by the association of cholesterol and lecithin in the presence of water. The ternary diagram of Figure 4 is relative to these systems. Here only the lamellar liquid crystalline phase is obtained (region 1< in Figure 4). This phase is already given by lecithin alone, which can absorb up to 55% water. Cholesterol can be incorporated within this lamellar phase up to the proportion of one molecule of choles-... 

Other conversion methods depend on the disruption of micelles containing water-insoluble compounds. For example, lipids e.g. lecithins can be reasonably well cosolubilized in micelles of sodium cholate or SDS. Dialysis slowly removes monomeric detergent molecules which dissociate away from the micelle resulting in a more concentrated lipid. Time and temperature controlled dialysis of the micelles finally yields monolamellar vesicles of uniform radii. ... 

The classic X-ray diffraction work of Small et al. [5,207,208] pointed out the existence of inverted (reverse) bile salt micelles within mixed bile salt-phospholipid liquid crystalline bilayers. The aggregates were considered to consist of 2-4 molecules (of cholate) with their hydrophilic sides facing inwards bound by hydrogen bonds between the hydroxyl groups, leaving their hydrophobic sides facing outwards to interact with the acyl chains of the phospholipid. At saturation, about 1 molecule of cholate was present for every 2 molecules of lecithin. Appreciably more bile salts... 

In this dissolution model, resistance occurs at the crystal-solution interface. When dissolution rate constant is plotted against angular velocity the positive intercept on the vertical axis indicates interfacial resistance (Figure 1)[9]. Detachment of Ch molecules from the surface of the cholesterol disk (or Ch stone) is a slow process and can be influenced by the presence of lecithin in BS micelles. Higuchi et al. have shown that dissolution of ChM crystals by cholate-lecithin solutions is unaffected by variations of angular... 

Ekwall and Baltcheffsky [265] have discussed the formation of cholesterol mesomorphous phases in the presence of protein-surfactant complexes. In some cases when cholesterol is added to these solutions a mesomorphous phase forms, e.g. in serum albumin-sodium dodecyl sulphate systems, but this does not occur in serum albumin-sodium taurocholate solutions [266]. Cholesterol solubility in bile salt solutions is increased by the addition of lecithin [236]. The bile salt micelle is said to be swollen by the lecithin until the micellar structure breaks down and lamellar aggregates form in solution the solution is anisotropic. Bile salt-cholesterol-lecithin systems have been studied in detail by Small and coworkers [267-269]. The system sodium cholate-lecithin-water studied by these workers gives three paracrystalline phases I, II, and III shown in Fig. 4.37. Phase I is equivalent to a neat-soap phase, phase II is isotropic and is probably made up of dodecahedrally shaped lecithin micelles and bile salts. Phase III is of middle soap form. The isotropic micellar solution is represented by phase IV. The addition of cholesterol in increasing quantities reduces the extent of the isotropic... 

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