Natural amphiphiles, phospholipids

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.

Vesicles for use as materials can be divided into two categories naturally occurring vesicles, or liposomes, which are composed of natural amphiphiles, usually phospholipids and polymer vesicles, which are generally composed of block copolymers. 

Phospholipids exhibit an excellent abihty to form liposome structures and are common in naturally-occurring cell membranes. The reason that nature uses phospholipids in the cell membrane is partly based on evolution-related biosynthetic requirements. From a physicochemical point of view, an amphiphile can form a liposome-hke supramolecular assembly as long as the amphiphile satisfies various structural requirements. Indeed, it has been found that a much simpler molecule - an ammonium salt with two long alkyl tails - can also form liposome-like assembhes. Therefore, structures simi-... 

Lipids. After 15 years of systematic measurement, interactions between amphiphilic assemblies, particularly between phospholipid bilayer membranes, are as well elaborated as for any class of materials (for a recent review, see reference 6). By their very nature, amphiphilic molecules self-assemble in water into structures that separate polar group-water compartments from hydrophobic compartments. Aqueous spaces in these assemblies swell and shrink under the combined influence of all the forces that stabilize the molecular assemblies as well as those that determine their association. Because the subject has been so thoroughly reviewed, we need mention only general points here. 

Besides naturally occurring phospholipids also synthetic surfactants were demonstrated to form globular aggregates. In general, double chain amphiphiles are better suited for vesicle formation than single chain ones. 

Artificially prepared vesicles made of amphiphilic molecules are named liposomes (originated from the Greek words Upos fat, and soma body), and were discovered in 1961 by Alec D. Bangham. They differ from micelles because of their bounded bilayer architecture, which determines an inside and an outside aqueous domain with, under osmotically balanced conditions, a spherical shape. The nature of the bilayer is often composed of pure or mixed naturally derived phospholipids (e.g., phosphatidyl choline). 

However, the value of y of surfactant solutions decreases to 30 mN/m with surfactant concentration around mmol/L (range of 1-10 g/L). Soaps have been used by mankind for many centuries. In biology, one finds a whole range of natural amphiphile molecules (bile salts, fatty acids, cholesterol and other related molecules, phospholipids). In fact, many important biological structures and functions are based on amphiphile molecules. 

Natural amphiphiles are often lipids. In this chapter, we focus on polar lipids with an amphiphilic character, such as phospholipids (see the next section for examples). The latter, together with proteins, make np cell membranes that are formed from self-assembled bilayer structures. A key feature of amphiphilic membranes in biological systems is that they are ordered and yet fluid, allowing the transport of material across them. The properties of membranes are considered in Section 4.11 of this chapter. 

A typical biomembrane consists largely of amphiphilic lipids with small hydrophilic head groups and long hydrophobic fatty acid tails. These amphiphiles are insoluble in water (<10 ° mol L ) and capable of self-organization into uitrathin bilaycr lipid membranes (BLMs). Until 1977 only natural lipids, in particular phospholipids like lecithins, were believed to form spherical and related vesicular membrane structures. Intricate interactions of the head groups were supposed to be necessary for the self-organization of several ten thousands of... 

Phospholipids or similar water-insoluble amphiphilic natural substances aggregate in water to form bilayer liquid crystals which rearrange when exposed to ultrasonic waves to give spherical vesicles. Natural product vesicles are also called liposomes. Liposomes, as well as synthetic bilayer vesicles, can entrap substances in the inner aqueous phase, retain them for extended periods, and release them by physical process. 

An ability to penetrate lipid bilayers is a prerequisite for the absorption of drugs, their entry into cells or cellular organelles, and passage across the blood-brain barrier. Due to their amphiphilic nature, phospholipids form bilayers possessing a hydrophilic surface and a hydrophobic interior (p. 20). Substances may traverse this membrane in three different ways. 

In all three cases amphiphiles orient spontaneously to form structures resembling the phospholipid arrangement in biomembranes. These membrane models allow a variety of investigations of physical membrane properties which could not be conducted with the complex natural systems. 

A decrease in occupied area of the head group results in an increase in packing density of the molecules (45) exhibits only an expanded phase, (46) both a liquid and a solid-like phase, and (47) forms only a condensed film. Monolayer properties of many natural phospholipids and synthetic amphiphiles are described in the literature37 38. Especially the spreading behaviour of diacetylenic phospholipids at the gas-water interface was recently described by Hupfer 120). 

As an example of an asymmetric membrane integrated protein, the ATP synthetase complex (ATPase from Rhodospirillum Rubrum) was incorporated in liposomes of the polymerizable sulfolipid (22)24). The protein consists of a hydrophobic membrane integrated part (F0) and a water soluble moiety (Ft) carrying the catalytic site of the enzyme. The isolated ATP synthetase complex is almost completely inactive. Activity is substantially increased in the presence of a variety of amphiphiles, such as natural phospholipids and detergents. The presence of a bilayer structure is not a necessary condition for enhanced activity. Using soybean lecithin or diacetylenic sulfolipid (22) the maximal enzymatic activity is obtained at 500 lipid molecules/enzyme molecule. With soybean lecithin, the ATPase activity is increased 8-fold compared to a 5-fold increase in the presence of (22). There is a remarkable difference in ATPase activity depending on the liposome preparation technique (Fig. 41). If ATPase is incorporated in-... 

Lysophosphatidilo lipids These are amphiphilic surfactants produced in a natural way from phospholipids by phospholipases. Their mechanism of action as a promoter is not fully understood. It is supposed that, like other surfactants, they can affect intracellular proteins and polar groups of phospholipids in intercellular spaces, which may favor the formation of channels permitting the penetration of water and substances dissolved therein [45]. 

Very recently however, a new exciting class of biohybrid amphiphiles, the giant amphiphiles, has been developed. These giant amphiphiles consist of a natural biomacromolec-ular head group, such as an enzyme or protein and a polymeric tail. They possess the same hydrophilic/hydrophobic character as their phospholipid molecular counterparts but have dimensions many times larger (Section 4.3). 

A large number of macromolecules possess a pronounced amphiphilicity in every repeat unit. Typical examples are synthetic polymers like poly(l-vinylimidazole), poly(JV-isopropylacrylamide), poly(2-ethyl acrylic acid), poly(styrene sulfonate), poly(4-vinylpyridine), methylcellulose, etc. Some of them are shown in Fig. 23. In each repeat unit of such polymers there are hydrophilic (polar) and hydrophobic (nonpolar) atomic groups, which have different affinity to water or other polar solvents. Also, many of the important biopolymers (proteins, polysaccharides, phospholipids) are typical amphiphiles. Moreover, among the synthetic polymers, polyamphiphiles are very close to biological macromolecules in nature and behavior. In principle, they may provide useful analogs of proteins and are important for modeling some fundamental properties and sophisticated functions of biopolymers such as protein folding and enzymatic activity. 

These aspects of MDR as well as the presented data underline the statement that permeability properties of compounds - especially their amphiphilic nature - cannot sufficiently be described through their partition coefficient in the octanol-buffer system because of special interactions with the phospholipids constituting the membrane. 

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