Bilayer, amphiphilic molecules

Liposomes, Vesicles and Cast Films - Supramolecular Assemblies Based on Lipid Bilayers Amphiphilic molecules or lipid molecules sometimes form double-layer structures. This structure is called a bilayer structure, and it can be used to model a cell membrane. 

Two principal routes of passive diffusion are recognized transcellular (la —> lb —> lc in Fig. 2.7) and paracellular (2a > 2b > 2c). Lateral exchange of phospholipid components of the inner leaflet of the epithelial bilayer seems possible, mixing simple lipids between the apical and basolateral side. However, whether the membrane lipids in the outer leaflet can diffuse across the tight junction is a point of controversy, and there may be some evidence in favor of it (for some lipids) [63]. In this book, a third passive mechanism, based on lateral diffusion of drug molecules in the outer leaflet of the bilayer (3a > 3b > 3c), wih be hypothesized as a possible mode of transport for polar or charged amphiphilic molecules. 

The charge-state section highlighted the value of Bjerrum plots, with applications to 6- and a 30-pKa molecules. Water-miscible cosolvents were used to identify acids and bases by the slope in the apparent pKa/wt% cosolvent plots. It was suggested that extrapolation of the apparent constants to 100% methanol could indicate the pKa values of amphiphilic molecules embedded in phospholipid bilayers, a way to estimate pAi m using the dielectric effect. 

The effect characteristic of a multi-chain hydrophobe, that is, increase in the cmc and simultaneous decrease in the cloud point, appears to be inconsistent with the well-known HLB concept in surfactants. Tanford has pointed out that based on geometric considerations of micellar shape and size, amphiphilic molecules having a double-chain hydrophobe tend to form a bilayer micelle more highly packed rather than those of single-chain types ( ). In fact, a higher homologue of a,a -dialkylglyceryl polyoxyethylene monoether has been found to form a stable vesicle or lamellar micelle (9 ). Probably, the multi-chain type nonionics listed in... 

The most fascinating characteristic some amphiphile molecules exhibit is that, when mixed with water, they form self-assembly structures. This was already discussed in Chapter 2 on micelle formation. Since most of the biological lipids also exhibit self-assembly structure formation, this subject has been given much attention in the literature (Birdi, 1999). Lipid monolayer studies thus provide a very useful method to obtain information about SAM formation, both concerning technical systems and cell bilayer structures. 

These results leave little doubt that specific clustering of amphiphilic molecules in bilayer membranes can take place. An important question... 

Liposomes and micelles are lipid vesicles composed of self-assembled amphiphilic molecules. Amphiphiles with nonpolar tails (i.e., hydrophobic chains) self-assemble into lipid bilayers, and when appropriate conditions are present, a spherical bilayer is formed. The nonpolar interior of the bilayer is shielded by the surface polar heads and an aqueous environment is contained in the interior of the sphere (Figure 10.3A). Micelles are small vesicles composed of a shell of lipid the interior of the micelle is the hydrophobic tails of the lipid molecules (Figure 10.3B). Liposomes have been the primary form of lipid-based delivery system because they contain an aqueous interior phase that can be loaded with biomacromolecules. The ability to prepare liposomes and micelles from compounds analogous to pulmonary surfactant is frequently quoted as a major advantage of liposomes over other colloidal carrier systems. 

The lipid part of the membrane is essentially a two-dimensional liquid in which the other materials are immersed and to which the cytoskeleton is anchored. This last statement is not totally correct, as some membrane bound enzymes require the proximity of particular lipids to function properly and are thus closely bound to them. Simple bilayers formed from lipids in which both hydrocarbon chains are fully saturated can have a highly ordered structure, but for this reason tend to be rigid rather than fluid at physiological temperatures. Natural selection has produced membranes which consist of a mixture of different lipids together with other amphiphilic molecules such as cholesterol and some carboxylic acids. Furthermore, in many naturally occurring lipids, one hydrocarbon chain contains a double bond and is thus kinked. Membranes formed from a mixture of such materials can retain a fluid structure. The temperature at which such membranes operate determines a suitable mixture of lipids so that a fluid but stable structure results at this temperature. It will be seen that the lipid part of a membrane must, apart from its two-dimensional character, be disordered to do its job. However, the membrane bound proteins have a degree of order, as will be discussed below. 

Approaches to artificial ion channels have, for instance, made use of macrocyclic units [6.72,6.74] (see also below), of peptide [8.183-8.185] and cyclic peptide [8.186] components, of non-peptidic polymers [8.187] and of various amphiphilic molecules [6.11, 8.188, 8.189]. The properties of such molecules incorporated in bilayer membranes may be studied by techniques such as ion conductance [6.69], patch-clamp [8.190] or NMR [8.191, 8.192] measurements. However, the nature of the superstructure formed and the mechanism of ion passage (carrier, channel, pore, defect) are difficult to determine and often remain a matter of conjecture. 

Diacyllipid-polyethyleneoxide conjugates have been introduced into the controlled drug delivery area as polymeric surface modiLers for liposomes (Klibanov et al., 1990). Being incorporated into the liposome membrane by insertion of their lipidic anchor into the bilayer, such molecules can ster-ically stabilize the liposome against interaction with certain plasma proteins in the blood that results in signiLcant prolongation of the vesicle circulation time. The diacyllipid-PEO molecule itself represents a characteristic amphiphilic polymer with a bulky hydrophilic (PEO) portion and a very short but extremely hydrophobic diacyllipid part. Typically, for other PEO-containing amphiphilic block... 

Lipid bilayer Amphipathic (or amphiphilic) molecules contain both hydrophilic (water-... 

The ability of the above mentioned substances to self-organize into bilayer membranes is caused by their amphiphility. During the formation of the vesicles the amphiphilic molecules orient themselves in such a way that their polar heads contact aqueous phases outside and inside the vesicle, while their nonpolar tails are directed towards the interior of the bilayer as shown in Fig. 2c. Vesicles can be classified in multilamellar, small unilamellar (d = 200-500 A) and large unilamellar (d = 1000-5000 A) ones. Since these are small unilamellar vesicles that are typically used for studying PET, in further discussion the term vesicle will always refer to the vesicles of this type, unless otherwise specified. 

Fluorescence techniques have also been used to determine the localization of molecules in membranes. Using this technique, the localization of the linear dye molecule 3,3 -diethyloxadicarboxyamine iodide (DODCI) in lipid bilayer vesides was determined as a function of lipid chain length and unsaturation. It was found that the fraction of the dye in the interior region of the membrane was decreased as a function of chain length in the order C12 > C14 > C16 > C18. In unsaturated lipids it was Ci4 i > C14 0 > C16 1 > C16 0, which is in agreement with the general observation that the penetration of amphiphilic molecules into the interior of membranes increases with an increase in the fluidity of the membrane structure [59]. 

Although it is clear that complex lipids can be synthesized under laboratory simulations using pure reagents, the list of required ingredients does not seem plausible under prebiotic conditions. Therefore, it is unlikely that early membranes were composed of complex lipids such as phospholipids and cholesterol. Instead, there must have been a source of simpler amphiphilic molecules capable of self-assembly into membranes. One possibility is lipidlike fatty acids and fatty alcohols, which are products of FTT simulations of prebiotic geochemistry [12] and are also present in carbonaceous meteorites. Furthermore, as will be discussed later, these compounds form reasonably stable lipid bilayer membranes by self-assembly from mixtures (Fig. 4a). 

Fig. 4 Stability and permeability of self-assembled amphiphilic structures. Amphiphilic molecules such as fatty acids having carbon chain lengths of 9 or more carbons form bilayer membranes when sufficiently concentrated, a Pure bilayers of ionized fatty acid are relatively unstable but become markedly more stable as long chain alcohols are added, b Dimensions of the amphiphile also play a role. Shorter chain amphiphiles (9-10 carbons) are less able to form bilayers, while those of intermediate chain length (12-14 carbons) produce stable bilayers that also are permeable to ionic and polar solutes. Longer chain lengths (16-18 carbons) produce bilayers that are increasingly less permeable to solutes [48]...

What physical properties are required if a molecule is to become incorporated into a stable bilayer As discussed earlier, all bilayer-forming molecules are amphiphiles, with a hydrophilic head and a hydrophobic tail on the same molecule. If amphiphilic molecules were present in the mixture of organic compounds available on the early Earth, it is not difficult to imagine that their self-assembly into molecular aggregates was a common process. 

Bile salts are amphiphilic molecules that are surface active and self-associate to form micelles in aqueous solution. They increase corneal permeability by changing the rheological properties of the bilayer [231], A number of bile salts such as deoxy-cholate, taurodeoxycholate, and glycocholate have been tested so far, and it was suggested, that a difference in their physicochemical properties (solubilizing activity, lipophilicity, Ca2+ sequestration capacity) is probably related to their performance as permeability-enhancing agents [36]. 

Microscopic foam films are most successfully employed in the study of surface forces. Since such films are small it is possible to follow their formation at very low concentrations of the amphiphile molecules in the bulk solution. On the other hand, the small size permits studying the fluctuation phenomena in thin liquid films which play an important role in the binding energy of amphiphile molecules in the bilayer. In a bilayer film connected with the bulk phase, there appear fluctuation holes formed from vacancies (missing molecules) which depend on the difference in the chemical potential of the molecules in the film and the bulk phase. The bilayer black foam film subjected to different temperatures can be either in liquid-crystalline or gel state, each one being characterised by a respective binding energy. 

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