Micelles, phospholipids

Whereas soaps may form any of the layer or micelle structures in Figure 10.31, the favoured structure of phospholipids in aqueous media is the bilayer (lamellar micelle). Phospholipid bilayers have a great tendency to close in on themselves to form bilayer spherical micelles which are known as liposomes or phospholipid vesicles (Figure 10.32a). These may lie in the size range 500-10,000 A diameter. 

Like the soap ions, phospholipids have the intriguing property of self-assembly into groups. Soap ions in water naturally group themselves into micelles. Phospholipids, however, have a chemical structure that, while similar to that of soap ions, precludes their assembly into micelles. Rather, they form layer structures. And under the right circumstances, a layer may fold back on itself like the skin of a basketball to enclose a space, forming a vesicle. 

Such linear free energy relationships are available for alkyl sulphates and for tire C4 to C9 homologues of tire dialkanoyl lecitliins (see table C2.3.3 for stmcture). Most of tire naturally occurring phospholipids are too insoluble to fonn micelles, but tire lower alkanoyl lecitliins, also known as phosphotidylcholines, do fonn micelles. The ernes for tliese homologues are listed in table C2.3.6. The approximately linear free energy relationship between tire alkyl chain iengtli and log cmc is given by ... 

Fig. 13. Lyotropic liquid crystal structures (a) micelle formed by a typical soap (b) vesicle formed by a typical phospholipid.

Phospholipids are found widely in both plant and animal tissues and make up approximately 50% to 60% of cell membranes. Because they are like soaps in having a long, nonpolar hydrocarbon tail bound to a polar ionic head, phospholipids in the cell membrane organize into a lipid bilayer about 5.0 nm (50 A) thick. As shown in Figure 27.2, the nonpolar tails aggregate in the center of the bilayer in much the same way that soap tails aggregate in the center of a micelle. This bilayer serves as an effective barrier to the passage of water, ions, and other components into and out of cells. 

Figure 14-22. Formation of lipid membranes, micelles, emulsions, and liposomes from am-phipathic lipids, eg, phospholipids.

The amphipathic character of phospholipids suggests that the two regions of the molecule have incompatible solubihties however, in a solvent such as water, phos-phohpids organize themselves into a form that thermodynamically serves the solubihty requirements of both regions. A micelle (Figure 41 ) is such a structure the hydrophobic regions are shielded from water, while the hydrophilic polar groups are immersed in the aqueous environment. However, micelles are usually relatively small in size (eg, approximately 200 nm) and thus are hmited in their potential to form membranes. 

The major lipids in the diet are triacylglycerols and, to a lesser extent, phospholipids. These are hydrophobic molecules and must be hydrolyzed and emulsified to very small droplets (micelles) before they can be absorbed. The fat-soluble vitamins— A, D, E, and K— and a variety of other lipids (including cholesterol) are absorbed dissolved in the lipid micelles. Absorption of the fat-soluble vitamins is impaired on a very low fat diet. 

Figure 7.22b shows that hydrophilic molecules, those with log Kj < 1, are much more permeable in octanol than in olive oil. The same may be said in comparison to 2% DOPC and dodecane. Octanol appears to enhance the permeability of hydrophilic molecules, compared to that of DOPC, dodecane, and olive oil. This is dramatically evident in Fig. 7.7, and is confirmed in Figs. 7.8c and 7.22b. The mechanism is not precisely known, but it is reasonable to suspect a shuttle service may be provided by the water clusters in octanol-based PAMPA (perhaps like an inverted micelle equivalent of endocytosis). Thus, it appears that charged molecules can be substantially permeable in the octanol PAMPA. However, do charged molecules permeate phospholipid bilayers to any appreciable extent We will return to this question later, and will cite evidence at least for a partial answer. 

The transport properties of the acids did not respond significantly to the presence of the sink. This may be because at pH 7.4 the acids are negatively charged, as are the phospholipid membranes and also the surfactant micelles electrostatic repulsions balanced out the attractive forces due to increased membrane lipophilicity. Lowered surface pH may also play a balancing role [457]. 

Highly insoluble molecules are in part transported in the GIT by partitioning into the mixed micelles injected into the lumen from the biliary duct in the duodenum (Fig. 2.3). Mixed micelles consist of a 4 1 mixture of bile salts and phospholipids (Fig. 7.13). In contrast, at the point of absorption in the BBB, highly insoluble molecules are transported by serum proteins. This distinction is expected to be important in in vitro assay modeling. The use of simulated intestinal fluids is appealing. 

Phospholipids are amphiphilic substances i.e. their molecules contain both hydrophilic and hydrophobic groups. Above a certain concentration level, amphiphilic substances with one ionized or polar and one strongly hydrophobic group (e.g. the dodecylsulphate or cetyltrimethylammonium ions) form micelles in solution these are, as a rule, spherical structures with hydrophilic groups on the surface and the inside filled with the hydrophobic parts of the molecules (usually long alkyl chains directed radially into the centre of the sphere). Amphiphilic substances with two hydrophobic groups have a tendency to form bilayer films under suitable conditions, with hydrophobic chains facing one another. Various methods of preparation of these bilayer lipid membranes (BLMs) are demonstrated in Fig. 6.10. 

Fig. 10.5 Schematic diagrams a micelle consisting of ionized fatty acid molecules, a phospholipid bilayer and the vesicle bilayer of a liposome...

Figure 22.1 The amphiphilic nature of phospholipids in solution drives the formation of complex structures. Spherical micelles may form in aqueous solution, wherein the hydrophilic head groups all point out toward the surrounding water environment and the hydrophobic tails point inward to the exclusion of water. Larger lipid bilayers may form by similar forces, creating sheets, spheres, and other highly complex morphologies. In non-aqueous solution, inverted micelles may form, wherein the tails all point toward the outer hydrophobic region and the heads point inward forming hexagonal shapes.

Dubertret, B., Skourides, P., Norris, D.J., Noireaux, V., Brivanlou, A.H., and Libchaber, A. (2002) In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298, 1759-1762. 

Sanders CR, Hare B J, Howard KP, Prestegard JH (1994) Magnetically-oriented phospholipid micelles as a tool for the study of membrane-associated molecules. Prog Nucl Magn Reson Spectrosc 26 421 144... 

Nieh MP, Raghunathan VA, Glinka CJ, Harroun TA, Pabst G, Katsaras J (2004) Magnetically alignable phase of phospholipid bicelle mixtures is a chiral nematic made up of wormlike micelles. Langmuir 20 7893-7897... 

In 1977, Kellogg and Fridovich [28] showed that superoxide produced by the XO-acetaldehyde system initiated the oxidation of liposomes and hemolysis of erythrocytes. Lipid peroxidation was inhibited by SOD and catalase but not the hydroxyl radical scavenger mannitol. Gutteridge et al. [29] showed that the superoxide-generating system (aldehyde-XO) oxidized lipid micelles and decomposed deoxyribose. Superoxide and iron ions are apparently involved in the NADPH-dependent lipid peroxidation in human placental mitochondria [30], Ohyashiki and Nunomura [31] have found that the ferric ion-dependent lipid peroxidation of phospholipid liposomes was enhanced under acidic conditions (from pH 7.4 to 5.5). This reaction was inhibited by SOD, catalase, and hydroxyl radical scavengers. Ohyashiki and Nunomura suggested that superoxide, hydrogen peroxide, and hydroxyl radicals participate in the initiation of liposome oxidation. It has also been shown [32] that SOD inhibited the chain oxidation of methyl linoleate (but not methyl oleate) in phosphate buffer. 

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