Amphiphilic membrane-forming

Brettreich M, Burghardt S, Bottcher C, Bayerl T, Bayerl S, Hirsch A (2000) Globular amphiphiles membrane-forming hexaadducts of C60. Angew Chem hit Ed 39 1845-1848... 

Another important area of progress is the enlargement of the scope of the structure of aqueous aggregates. The bilayer membrane formed from dialkyl amphiphiles belongs to a new class of the aqueous aggregate, totally different from the conventional surfactant micelle. A trialkylammonium compound gives yet another type of aggregation. 

Micelles are capable of self-replication if an appropriate chemical reaction occurs within the micelle itself that produces more of the same amphiphile that forms the micelle. Such self-replication has been demonstrated for both ordinary micelles in an aqueous medium [139] as well as for reverse micelles, [140] which are spherules of water stabilized by an amphiphile in an organic solvent. Some of the prebiotic potentialities of replicating membranous vesicles have been investigated, [141] and they have been characterized as "minimum protocells. [142]... 

Cholinesterases are subdivided into acetylcholinesterase and cholinesterase, one with a narrow, the other with broad substrate specificity [109-112], Both enzymes exist in multiple molecular forms distinguishable by their subunits association (Fig. 2.4). The hydrodynamic properties of these associations have allowed globular (G) and asymmetric (A) forms to be distinguished. The G forms can be hydrophilic (water-soluble, and excreted into body fluids) or amphiphilic (membrane-bound). The homomeric class exists... 

Fig. 2.4. Schematic model of the molecular polymorphism of acetylcholinesterase and cholinesterase [110][112a]. Open circles represent the globular (G) catalytic subunits. Disulfide bonds are indicated by S-S. The homomeric class exists as monomers (Gl), dimers (G2), and tetramers (G4) and can be subdivided into hydrophilic (water-soluble) and amphiphilic (membrane-bound) forms. The G2 amphiphilic forms of erythrocytes have a glycophospholipid anchor. The heteromeric class exists as amphiphilic G4 and as asymmetric forms (A) containing one to three tetramers. Thus, heteromeric G4 forms found in brain are anchored into a phospholipid membrane through a 20 kDa anchor. The asymmetric A12 forms have three hydrophilic G4 heads linked to a collagen tail via disulfide bonds.

It has been reported that a variety of single-chain amphiphiies spontaneously produce stable, membrane-forming aggregates when dispersed in water 258 260). Dialky 1-amphiphile l-III (l or d means l- or D-configuration of amino acid unit in compound III, respectively), which was prepared by condensation of didodecyl L-glutamate and p-(4-bromobutoxy)benzoic acid and the subsequent quarterization with tri-methylamine, produces bilayer vesicles in water as probed by electron microscopy 251 >. 

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. 

Shinkai and coworkers prepared numerous novel amphiphilic crowns (Shinkai, 1990) and incorporated them into membranes, formed membranes from them, or used them in liquid crystalline assemblies to control properties (He et al., 1990). Interest in this area continues. Four chiral amphiphilic crown ethers were recently reported that recognize enantiomeric amino acids when examined as Langmuir films (Badis et al., 2004). Finally, it is interesting to note that liposomes formed from amphiphiles (e.g., crown ethers) having neutral headgroups (i. e., niosomes) have been studied as drug delivery vehicles (Uchegbu and Vyas, 1998). 

The membrane formed by the self-assemby of an amphiphilic ABA triblock copolymers was used by Meier and coworkers to reconstitute membrane proteins in artificial... 

It is commonly assumed that transfer processes can be modeled by bulk phase thermodynamics and that surface or interfacial effects are negligible. These assumptions may, in the case of partitioning into amphiphilic structures formed by micelles or bilayer membranes, not always be appropriate. These interfacial solvents have a large surface to volume ratio, similar to interfacial solvents used in reversed-phase liquid chromatography. The partitioning into such phases is the basis of the chromatographic separation. 

Holmes, T., Zhang, S., Rich, A., Dipersio, C.M., and Lockshin, C. Stable Macroscopic Membranes Formed by Self-Assembly of Amphiphilic Peptides and Uses Therefor, 94-293284 5955343 (1999). 

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-... 

U.S. Patent No. 6 800 481, Stable macroscopic membranes formed by self-assembly of amphiphilic peptides and uses therefor, 2004. 

Two amphiphiles with a reactive dye system as head groups, namely p-phenylenediamine and 4,4 -bipyridinium salts, have already been mentioned. Other such membrane-forming amphiphiles were modelled following natural photosynthetic membrane systems. Carotenoid amphiphiles are accessible from the cheap natural bolaamphiphile bixin, which carries a carboxylic acid on one end and a methyl ester on the other. A variety of orange-coloured bolaamphi-... 

Electron microscopy provides perfect pictures of vacuum collapsed vesicle membranes after negative staining with heavy metal salts. BLMs appear usually as collapsed balls, MLMs often as flat disks (see Figure 4.29). There is no requirement for double-chain amphiphiles in order to form vesicles. The same single-chain amphiphiles which form micelles also form vesicles if their charge is neutralized. This was practised, for example, via the protonation of soaps or through addition of an amphiphilic counterion. In both cases, fatty acids function perfectly well in the form of vesicles. 

Certain pathological cells produce excessive amounts of a particular enzyme, e.g. neuroblastoma/acetylcholinesterase. If such an enzyme is capable of breaking open specially designed vesicles which encapsulate a cytotoxic drug, then cell selective therapeutic activity can be achieved. The double-chain amphiphile 23 forms vesicles and incorporates an acetylcholine-like head group which was readily hydrolyzed by acetylcholinesterase (AcE). The primary alcohol then ejected one of the two tails and the remaining single chain amphiphile destroyed the bilayer membrane-bound fluorescent dyes were set free within seconds. ... 

Prepolymerized lipids form vesicles only if the disentanglement of the polymer main chain ( = hack hone) and the membrane forming side-chains is simplified hy a hydrophilic spacer between them . Efficient decouplings of the motions of the polymeric chain and the polymeric bilayer are thus achieved and stable liposomes with diameters of around 500 nm were formed upon ultrasonication (Figure 4.28a). Their bilayer showed a well-defined melting behaviour in DSC. The ionene polymer with C12, C16 and C20 intermediate chains also produced vesicles upon sonication (Figure 4.28b). Here, the amphiphilic main chain is obviously so simple that ordering to form membranes produces no problems whatsoever . ... 

Emulsifiers are necessary to allow water and lipids to combine. A surfactant is an amphiphilic molecule that has affinities for fats as well as water and that can be incorporated into lamellar lipid structures (e.g. cell walls). Surfactants increase the fluidity of the lipid structures by partitioning into the lipid membranes, as their lateral interactions with the membrane-forming lipids reduce the force of their attractive interaction. The mobility of the membrane lipids increases considerably in a similar manner to when a liquid crystal is converted into a gel. Finally, lipids can be seen to micellize or simply dissolve. Membranes lose their relative impermeability. See Figure 5.16. 

Could early membrane-forming amphiphiles have simply been polyprenyl phosphates, following the Strasbourg scenario (Birault et al., 1996) ... 

Artificial enzymes may be divided into two categories semisynthetic artificial enzymes and synthetic artificial enzymes. Semisynthetic artificial enzymes are partly prepared by biological systems. Catalytic antibodies are typical examples of semisynthetic artificial enzymes. Semisynthetic artificial enzymes are also prepared by modification of a known protein or enzyme at a defined site with a cofactor or new functional group. Synthetic artificial enzymes are prepared totally by synthetic methods. Synthetic artificial enzymes may be either relatively small molecules with well-characterized structures or macromolecules. The term syn-zymes has been coined to designate synthetic polymers with enzyme-like activities. In addition, synthetic artificial enzymes are also obtained with molecular clusters such as micelles and bilayer membranes formed by amphiphiles. 

In most cases, the amphiphilic polymers do not exhibit intrinsic fluorescence and therefore a dye needs to be encapsulated, or the vesicle membrane has to be stained. The first method requires encapsulation of a water-soluble fluorescent dye during vesicle formation followed by a subsequent exclusion of the dye from the extracellular space (e.g., by size exclusion chromatography, dialysis, ultrafiltration, or centrifugation). To stain the membrane either a fluorophore is covalently linked in a certain percentage to the membrane forming molecules, or a lipophilic probe is aggregated in the hydrophobic part of the membrane [116,146,175,176],... 

The formation of ether-type polar lipids that occur in the membranes of Archaea remains elusive. The enantiomeric glycerol-phosphate backbone, ether linkages, and isoprenoid chains are distinguishing features of archaeal lipids. Carbonaceous meteorites contain up to several percent of their mass as organic carbon, mainly polycyclic aromatic hydrocarbons. Material extracted from the Murchison meteorite by organic solvents contains amphiphiles that form membrane-like vesicles in aqueous solution. 

Many amphiphiles exist naturally and play a major role in biological processes. Phospholipids (Scheme 2) are of especial importance because their twin lipophilic groups allow them to form bilayers, so that they are the building blocks of membranes and they, and similar amphiphiles, will form vesicles in water [14,16,17]. 

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