Amphiphiles vesicle-forming

Phospholipid molecules form bilayer films or membranes about 5 nm in thickness as illustrated in Fig. XV-10. Vesicles or liposomes are closed bilayer shells in the 100-1000-nm size range formed on sonication of bilayer forming amphiphiles. Vesicles find use as controlled release and delivery vehicles in cosmetic lotions, agrochemicals, and, potentially, drugs. The advances in cryoelec-tron microscopy (see Section VIII-2A) in recent years have aided their characterization [70-72]. Additional light and x-ray scattering measurements reveal bilayer thickness and phase transitions [70, 71]. Differential thermal analysis... 

Recently, unique vesicle-forming (spherical bUayers that offer a hydrophilic reservoir, suitable for incorporation of water-soluble molecules, as well as hydrophobic wall that protects the loaded molecules from the external solution) setf-assembUng peptide-based amphiphilic block copolymers that mimic biological membranes have attracted great interest as polymersomes or functional polymersomes due to their new and promising applications in dmg delivery and artificial cells [ 122]. However, in all the cases the block copolymers formed are chemically dispersed and are often contaminated with homopolymer. 

Uchegbu and coworkers have studied the complexation and delivery of DNA using a unique poly(amino acid)-based polymer vesicle. A polymer of either poly (L-lysine) or poly(L-omithine) was functionalized with methoxy-poly(ethylene glycol) (mPEG) and hydrophobic palmitic acid chains to synthesize an amphiphilic triblock of either mPEG-6-poly(L-lysine)-6-palmitoyl or mPEG-Z>-poly(L-omithine)-6-palmitoyl. Vesicles formed from these polymers were complexed with DNA and showed improved transfection in vitro over poly(amino acid) complexed with DNA or DNA alone [82]. 

The vesicles made from lipid bilayers are analogous to polymersomes, which are vesicles formed from high molecular weight amphiphilic block copolymers [94—96], Unlike the micelles discussed earlier from the similar copolymer components, the presence of bilayer walls formed from the aggregation of hydrophobic domains provides new properties. They can be designed to respond, for example, by opening or by disassembly, to external stimuli such as pH, heat, light, and redox processes [97]. This makes them usable as scaffolds for cascade reactions, even those with combinations of enzymes [98, 99]. 

Several workers have introduced polymerizable groups into twin-tailed amphiphiles and formed vesicles by sonication. They then link the amphi-philes by initiating polymerization, either chemically or photochemically. The polymerized vesicles which are so generated show little tendency to fuse, and are much more stable than the vesicles formed by sonication or vaporization. They therefore have considerable potential for compartmentalizing reagents, although as with normal vesicles there is always the... 

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]... 

Figure 9.20 The amphiphilic character of vesicle-forming surfactant molecules the combination of oleic acid and oleate forms vesicles in the slightly alkaline pH range.

Earlier reports [50] showed that vesicles composed of oleic acid can grow and reproduce as oleoyl anhydride spontaneously hydrolyzed in the reaction mixture, thereby adding additional amphiphilic components (oleic acid) to the vesicle membranes. This approach has recently been extended by Hanczyc et al. [51], who prepared myristoleic acid membranes under defined conditions of pH, temperature, and ionic strength. The process by which the vesicles formed from micellar solutions required several hours, apparently with a rate-limiting step related to the assembly of nuclei of bilayer structures. However, if a mineral surface in the form of clay particles was present, the surface in some way catalyzed vesicle formation, reducing the time required from hours to a few minutes. The clay particles were spontaneously encapsulated in the vesicles. The authors further found that RNA bound to the clay was encapsulated as well. 

Significantly, the photoproducts of interstellar ice simulations also include amphiphilic compounds having self-assembly properties [31]. Figure 8 shows micrographs of Murchison vesicles, as well as vesicles formed by products of interstellar ice simulations and known fatty acid-fatty alcohol mixtures. It is clear that the vesicle-forming behavior of all of these amphiphiles is... 

The final challenge in modeling such systems will be to encapsulate an evolving ribozyme system [74,86,87] within vesicles formed from amphiphilic mixtures that are optimized for stability and permeability. It seems likely that one such mixture will have a set of properties that permit it to encapsulate a catalytic polymerase system and template, with sufficient permeability to allow substrate access to the enzyme at reasonable rates. Replication and ribozyme evolution would then occur in immensely large numbers... 

Jaeger et al. described [46] some novel double-chain vesicle-forming cleav-able amphipiles which were synthesized via ion-pairing of two oppositely charged head groups. These amphiphiles formed giant vesicles which cleave at the labile carbon-nitrogen double bond around pH 3. 

Engberts, J. B. F. N., and Hoekstra, D. (1995), Vesicle-forming synthetic amphiphiles, Biochim. Biophys. Acta, 1241, 323-340. 

It is also of interest to study the self-assembly of these inverted unimolecular dendritic micelles into vesicles in water at pH = 1 and at the air-water interface. In these vesicles, the dendrimers adopt a distorted conformation, far from spherical. These dendritic amphiphiles form a novel class of vesicle-forming surfactants [71] and introduce new perspectives towards a better understanding of the structure-property relation of amphiphiles on the one hand and dendrimers on the other hand. 

For vesicle-forming surfactants it is believed that the molecular area of the head group is roughly the same as that of the hydrophobic part of the amphiphile see Ref 64a. 

Sophisticated amphiphile designs allow us to develop bilayer-based organic-inorganic hybrids. In the example shown in Fig. 4.29, amphiphiles with alkoxysi-lane heads are used as bilayer-forming components. At the surface of the vesicle formed, cross-linked silanol groups form an inorganic silica-like structure. 

At the simplest level, SANS studies can be used to provide evidence of vesicle formation by determining the size (if the vesicles are relatively small) and the thickness of the bilayer of vesicles formed from molecules such as 1,2-di-C-octadecyl- and 1,2-di-O-hexadecyl-rac-glycerol-3-omega-methoxy-dodecaethy-lene glycol (2CigEi2 and 2Cie amphiphilic... 

CigNs amphiphile 8a forms 5 nm micelles in water with a cmc of 0.9 X 10 " M. In contrast, hyperextended C28N3 8b aggregates at concentrations too low to be determined by surface tension or Br NMR spectroscopy. Upon sonication, only vesicles were observed in this case. ... 

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. 

The vesicle-forming ethylenediaminediacetic acid derivative 10 complexes metal ions (e.g. Cu " ) from the aqueous phase. Since ftietal ions cannot generally penetrate hydrophobic vesicle membranes, literally any redox-active ions can be fixed to the inner and/or outer membrane surfaces. Cationic metallovesicles were also obtained from the double chain amphiphile 11 synthe-... 

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. ... 

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