Phospholipid vesicles intermediates

As an intermediate between solid supported layers and the inherent dynamic and nanostructured properties of phospholipid vesicle supports, silica and especially mesoporous silica nanoparticles may provide interesting platforms for dynamic bilayers. Previous studies have shown that stable bilayers can form on both amorphous [102] or functional silica [103, 104] and mesoporous nanoparticles [105] or membranes [106]. This type of biomimetic carrier has great potential as a type of trackable stabilized membrane capable of displaying cellular targeting elements in a close to natural configuration. 

Tew and Amt [92-94] have prepared amphiphilic meta-PPEs 58 and investigated their behavior at the air-water interface where they prefer an extended conformation. These PPEs are active in the lysis of phospholipid vesicles and might find application as bactericidal substances. While the derivative 58 with R = H forms clear solutions in water, the alkoxy-substituted congeners aggregate and precipitate out upon addition of water to their solution in DMSO. The structure of 58 in the solid state is assumed to be helical rather than extended. If acrylic ester substituents are placed on 59, it is possible to capture the helical intermediates by a photochemical 2-1-2 cycloaddition (Figure 6.2) [95,96]. The presence of a fixated helical structure was evident, because addition of chloroform to the cross-linked form did not... 

Peroxyl radicals are the species that propagate autoxidation of the unsaturated fatty acid residues of phospholipids (50). In addition, peroxyl radicals are intermediates in the metabolism of certain drugs such as phenylbutazone (51). Epoxidation of BP-7,8-dihydrodiol has been detected during lipid peroxidation induced in rat liver microsomes by ascorbate or NADPH and during the peroxidatic oxidation of phenylbutazone (52,53). These findings suggest that peroxyl radical-mediated epoxidation of BP-7,8-dihydrodiol is general and may serve as the prototype for similar epoxidations of other olefins in a variety of biochemical systems. In addition, peroxyl radical-dependent epoxidation of BP-7,8-dihydrodiol exhibits the same stereochemistry as the arachidonic acid-stimulated epoxidation by ram seminal vesicle microsomes. This not only provides additional... 

Polymerization in Bilayers. Upon irradiation with UV light the monomer vesicles are transferred to polymer vesicles (Figure 12.). In the case of the diyne monomers (2,5-9,12,13,14) the polyreaction can again be followed by the color change via blue to red except phospholipids (5,6), which turn red without going through the blue intermediate as observed in monolayers. The VIS spectra of these polymer vesicle dispersions are qualitatively identical to those of the polymer monolayers (Figure 13.). 

Intermediate-sized unilamellarvesicles (lUVs) have diameters of the order of magnitude of 100 nm, and are called large unilamellarvesicles (LUVs) if the size is more than 100 nm and they consist of a single bilayer. For unilamellarvesicles, the phospholipid content is related to the surface area of the vesicles, which is proportional to the square of the radius, while the entrapped volume varies with the cube of the radius. In addition, because of the Lnite thickness of the membrane (ca. 4 nm), as thf vesicles become smaller, their aqueous volume is further reduced since the phospholipids occupy more of the internal space. Consequently, for a given quantity of lipid, large unilamellar liposomes... 

Fig. 5 The snake PLA2 neurotoxin is depicted here as a snake, which binds to an active zone, i.e., a synaptic vesicle (SV) release site, and hydrolyses the phospholipids of the external layer of the presynaptic membrane (green) with formation of the inverted-cone shaped lysophospholipid (yellow) and the cone-shaped fatty acid (dark blue). Fatty acids rapidly equilibrate by trans-bilayer movement among the two layers of the presynaptic membrane. In such a way lysophospholipids, which induce a positive curvature of the membrane, are present in trans and fatty acid, which induce a negative curvature, are present also in cis, with respect to the fusion site. This membrane conformation facilitates the transition from a hemifusion intermediate to a pore. Thus, the action of the toxin promotes exocytosis of neurotransmitter (NT) (from the left to the right panel) and, for the same membrane topological reason, it inhibits the opposite process, i.e., the fission of the synaptic vesicle.

Introduction - Liposomes are vesicles composed of one or more lipid bilayers completely surrounding an internal aqueous space. They are usually composed of phospholipids either in pure form or In combination with other amphipathic molecules such as sterols, long chain bases or acids, or membrane proteins. The structure of liposomes varies from large (0.5->5y) multllamellar vesicles to small ( 300 A) unilamellar vesicles.2,3 More recently, new methods have been reported describing the formation of unilamellar vesicles of intermediate size. >5.6 xhe general properties of liposomes and their interaction with various macromolecules have been described in several reviews. ... 

The thermotropic phase transition temperature of a vesicle composed of a mixture of dipalmitoyl and dimyristoyl phosphatidylcholine (DPPC and DMPC, respectively) is intermediate between the phase transition temperatures of the single lipid vesicles and reflects the relative concentrations of the two lipids in the vesicle. This can be used to determine the rate of exchange of phosphatidylcholine between two unilamellar vesicles of initially pure phospholipid. 

This experimental approach has been used previously to study the spontaneous transfer of phospholipids between artificial membranes (Martin and MacDonald, 1976 Duckwitz-Peterlein et al., 1977). Xti et al. (1982) used the fluorescence anisotropy of diphenylhexatriene (DPH) in the phosphatidylcholine bilayer to measure the change in the physical state of DPPC and DMPC vesicles upon mixing in the presence of transfer protein. The fluorescent measurements were recorded at a temperature intermediate between the phase transition of the two initially pure vesicles. By using flow cytometry, it was possible to measure the fluorescence... 

A FIGURE 18-1 Overview of synthesis of major membrane lipids and their movement into and out of cells. Membrane lipids (e.g., phospholipids, cholesterol) are synthesized through complex multienzyme pathways that begin with sets of water-soluble enzymes and intermediates in the cytosol (D) that are then converted by membrane-associated enzymes into water-insoluble products embedded in the membrane (B), usually at the interface between the cytosolic leaflet of the endoplasmic reticulum (ER) and the cytosol. Membrane lipids can move from the ER to other organelles (H), such as the Golgi apparatus or the mitochondrion, by either vesicle-mediated or other poorly defined mechanisms. Lipids can move into or out of cells by plasma-membrane transport proteins or by lipoproteins. Transport proteins similar to those described in Chapter 7 that move lipids (0) include sodium-coupled symporters that mediate import CD36 and SR-BI superfamily proteins that can mediate... 

The interfacial stability of membrane lipids is a delicate balance of the amphipatic properties. To measure how the oxydation of cholesterol affects its membrane stability radiolabelled oxysterols were incorporated in phospholipid monolayers and their rate of release from the interface was determined (19). In the absence of vesicles there is no release measurable. The addition of serum high density lipoprotein or small unilamellar vesicles to the subphase brings about a hardly measurable release of cholesterol ( 0.5% h ). Much higher rates are found for 7-ketocholesterol, 7B-hydroxycholesterol, 7a-hydroxycholesterol, and 25-hydroxycholesterol in this order. This order is similar to their interaction with DOPC, that is, the most cholesterol-like oxysterol 7-ketocholesterol shows the lowest transfer rate and the oxysterol with the greater distance between the hydroxyl groups, 25-hydroxycholesterol, the highest transfer rate. The transfer measured is consistent with the involvement of a water soluble intermediate. 

Fig. 12. Model for apolipoprotein phospholipid association. In the left panel, the surface of a phospholipid-.cholesterol vesicle is depicted as a biphasic system in which homogeneous DMPC and 1 3 cholesterol-DMPC phases coexist. Each phase is bonded by interfacial lipid, and the interfacial lipid of each phase is separated from that of the other phase by a hole or channel defect. ApoA-I may insert into this defect to produce the initial lipid apoprotein intermediate on the right. The apoprotein is envisioned as a helical structure in the lipid matrix (from Pownall et al., 1979a).

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