Vesicles and Bilayer Membranes

Although extended planar bilayers are a thermodynamically favorable option for the association of some bulky surfactants in aqueous solution, under certain conditions it is more favorable to form closed bilayer systems, leading to the existence of membranes and vesicles. Such a situation arises from two basic causes (1) even large, highly extended planar bilayers possess edges along which the hydrocarbon core of the structure must be exposed to an aqueous environment, resulting in an 

Over the years it has been confirmed that geometric factors control the packing of surfactants and lipids into association structures. The concept has already been introduced, but warrants repetition in the current context for clarity. The packing propensity of a given amphiphilic stmcmre can be conveniently given by the critical packing parameter, denoted here as and given by 

Examples of materials that do not fit neatly into such a scheme may be found, but the general concepts are usually found to be valid. For surfactants and 

TABLE 5.1. Expected Aggregate Characteristics of Amphiphiles as Determined by Their Molecular Structure and Packing Parameter Pc 

Simple surfactants with single chains and relatively large head groups 0.33 Spherical or ellipsoidal micelles 

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This chapter discusses stereospecific intermolecular interactions in monolayers at the air-water interface, where surface-active molecules (surfactants) are partially oriented with respect to each other by the cooperative combination of interionic, hydrophobic, and hydrogenbonding forces. We believe that these reports should be of particular interest in relation to stereospecificity in assemblies such as micelles, vesicles, and bilayer membranes, where their significance has been largely ignored. 

Although the vast majority of surfactants form micelles of some kind in aqueous solution, some materials, because of their special structure or composition, will not associate in the normal way described above. They will, however, take part in other association processes to form equally interesting and important association colloids, including especially vesicles and bilayer membranes. 

The theoretical developments based on the effects of geometry on molecular aggregation have shown that physical characteristics of surfactants such as cmc, aggregate size and shape, and micellar size distribution (polydispersity) can be quantitatively described without relying on a detailed knowledge of the specific energetic components of the various molecular interactions. It is also useful in that it applies equally well to micelles, vesicles, and bilayer membranes the latter lie outside the normal models of association processes. For that reason, the geometric approach warrants a somewhat closer look. 

Phospholipid vesicles (and bilayers) composed of phospholipids with well-defined fatty acid side chains undergo a sharp transition from a crystallinelike state to an amorphous state as the temperature is raised.107 The transition temperature depends on the nature of the fatty acid side chains. For example, for C12 saturated fatty acid chains on lecithin the transition temperature is 0° and for C18 saturated fatty acid chains it is 58°C for unsaturated lecithins the transition temperature is below zero.107 For real membranes sharp phase transitions are not observed, because of the heterogeneous composition of the membrane. In the case of /3 hydroxybutyrate dehydrogenase, the enzymic activity apparently is not influenced by this phase transition as judged by the temperature dependence of the reaction rate. However, for some membrane-bound proteins, a plot of the reaction rate versus the reciprocal temperature... 

Figure 16.3 Neurotransmitter release, (a) Presynaptic nerve terminal containing vesicles and other organelles, (b) Neurotransmitter-containing vesicles are made of lipid bilayers. Associated proteins participate in the release process, (c) The vesicle associates with the presynaptic membrane via protein complexes that mediate release, (d) Release of neurotransmitter into the synapse is by protein-mediated fusion of vesicle and presynaptic membranes.

Aqueous molecular assemblies such as micelles and bilayer membranes are formed by the self-assembly of amphiphihc compounds (Figure 11.la, b) [10]. Aqueous micelles have been utihzed for a variety of apphcations in surfactant industry, including emulsification, washing, and extraction processes [11]. BUayer membranes are basic structural components of biomembranes, and their structures are maintained even in dilute aqueous media. This is in contrast to micelles that show dynamic equihbrium between aggregates and monomeric species. Thus bilayers are more stable and sophisticated self-assemblies, and they require suitable molecular design of the constituent amphiphiles. BUayer membranes and vesicles have wide-ranging applications, as exemphfied by drug dehvery [12], sensors [13], and bilayer-templated material synthesis [14]. 

Figure 11.1 Molecular structures and schematic illustrations of micelle and bilayer membranes (a) micelle, (b) bilayer membrane and vesicle, (c) CTAB, and (d) 2CnN. ...

Up until 1977, the non-covalent polymeric assemblies found in biological membranes rarely attracted any interest in supramolecular organic chemistry. Pure phospholipids and glycolipids were only synthesized for biophysical chemists who required pure preparations of uniform vesicles, in order to investigate phase transitions, membrane stability and leakiness, and some other physical properties. Only very few attempts were made to deviate from natural membrane lipids and to develop defined artificial membrane systems. In 1977, T. Kunitake published a paper on A Totally Synthetic Bilayer Membrane in which didodecyl dimethylammonium bromide was shown to form stable vesicles. This opened the way to simple and modifiable membrane structures. Since then, organic chemists have prepared numerous monolayer and bilayer membrane structures with hitherto unknown properties and coupled them with redox-active dyes, porous domains and chiral surfaces. Recently, fluid bilayers found in spherical vesicles have also been complemented by crystalline mono-... 

Equation [27] is valid for thin membranes and bilayer membranes with symmetrical inner and outer monolayers. This approximation breaks down in many vesicles of interest which are asymmetrical bilayers. The asymmetry is brought about by monolayers with different composition or exposed to different environments. In this case, the bending energy of Eq. [27] corresponds to that of the inner layer (i.e., dS = dS J. Similarly, the constraint A in Eq. [28] is i4j , the inner surface area. The exterior layer introduces an addi-... 

Small molecule aggregates such as micelles, bilayers, vesicles and biological membranes, form spontaneously by self-aggregation in aqueous solution [59,60]. As... 

This class of association colloids can be further divided into several subgroups, which include micelles, vesicles, microemulsions, and bilayer membranes. Each subgroup of association colloids plays an important role in many aspects of colloid and surface science, both as theoretical probes that help us to understand the basic principles of molecular interactions, and in many practical applications of those principles, including biological systems, medicine, detergency, crude-oil recovery, foods, pharmaceuticals, and cosmetics. Before undertaking a discussion of the various types of association colloids, it is important to understand the energetic and structural factors that lead to their formation. 

The structural and dynamic properties of polymerized surfactant aggregates such as detergent micelles, vesicles and bilayers have been studied extensively (32). From a biological aspect, it is of interest to determine in which way these structures mimic the properties of natural membranes (33). Most luminescent anisotropy studies of lipid rotation have employed the fluorescence characteristics of incorporated probes (34,35), as the time scales of lipid rotation are usually in the ns regime. However, a recent electron spin study using incorporated phospholipid spin-labels (36), indicated that rotation about the long axis of dimyristoyl-phosphatidylcholine (DMPC) lipids below the phase transition occurrs with time constants of about 60-100 is. Such values lie within the time domain of phosphorescence anisotropy measurements. 

The identity of the moiety (other than glycerol) esterified to the phosphoric group determines the specific phosphoHpid compound. The three most common phosphoHpids in commercial oils are phosphatidylcholine or lecithin [8002-45-5] (3a), phosphatidylethanolamine or cephalin [4537-76-2] (3b), and phosphatidjlinositol [28154-49-7] (3c). These materials are important constituents of plant and animal membranes. The phosphoHpid content of oils varies widely. Laurie oils, such as coconut and palm kernel, contain a few hundredths of a percent. Most oils contain 0.1 to 0.5%. Com and cottonseed oils contain almost 1% whereas soybean oil can vary from 1 to 3% phosphoHpid. Some phosphoHpids, such as dipaLmitoylphosphatidylcholine (R = R = palmitic R" = choline), form bilayer stmetures known as vesicles or Hposomes. The bdayer stmeture can microencapsulate solutes and transport them through systems where they would normally be degraded. This property allows their use in dmg deHvery systems (qv) (8). 

The other class of phenomenological approaches subsumes the random surface theories (Sec. B). These reduce the system to a set of internal surfaces, supposedly filled with amphiphiles, which can be described by an effective interface Hamiltonian. The internal surfaces represent either bilayers or monolayers—bilayers in binary amphiphile—water mixtures, and monolayers in ternary mixtures, where the monolayers are assumed to separate oil domains from water domains. Random surface theories have been formulated on lattices and in the continuum. In the latter case, they are an interesting application of the membrane theories which are studied in many areas of physics, from general statistical field theory to elementary particle physics [26]. Random surface theories for amphiphilic systems have been used to calculate shapes and distributions of vesicles, and phase transitions [27-31]. 

Phospholipids e.g. form spontaneously multilamellar concentric bilayer vesicles73 > if they are suspended e.g. by a mixer in an excess of aqueous solution. In the multilamellar vesicles lipid bilayers are separated by layers of the aqueous medium 74-78) which are involved in stabilizing the liposomes. By sonification they are dispersed to unilamellar liposomes with an outer diameter of 250-300 A and an internal one of 150-200 A. Therefore the aqueous phase within the liposome is separated by a bimolecular lipid layer with a thickness of 50 A. Liposomes are used as models for biological membranes and as drug carriers. 

H. E., and Crommelin, D. J. A., Characterization of liposomes (1987). The influence of extrusion of multilamellar vesicles through polycarbonate membranes on particle size, particle size distribution and number of bilayers, Int. J. Pharm.. 35, 263-274. 

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