Inverted hexagonal

FIG. 7 Structures of various liquid-crystalline phases of membrane lipids. (A) Normal hexagonal phase (Hi) (B) lamellar phase (C) inverted hexagonal phase (Hu). Cubic phases consisting of (D) spherical, (E) rod-shaped, and (F) lamellar units. The hydrocarbon regions are shaded and the hydrophilic regions are white. (Reprinted by permission from Ref. 11, copyright 1984, Kluwer Academic Publishers.)... 

FIG. 15 Cellular entry and intracellular kinetics of the cationic lipid-DNA complexes. Cationic lipid-DOPE liposomes form electrostatic complexes with DNA, and, in this case, also transferrin (Tf) is incorporated. Cellular uptake by endoc5dosis and endosomal acidification can be blocked with cytochaiasin B and bafilomycin Aj, respectively. DNA is proposed to be released at the level of endosomal wall after fusion of the carrier lipids with endosomal bilayer. This process is facilitated by the formation of inverted hexagonal DOPE phase as illustrated in the lower corner on the right. After its release to the C5doplasm DNA may enter the nucleus. (From Ref. 253. By permission of Nature Publishing Group.)... 

Fig. 9.3 The structure of LLC monomers, 1 and 2, and the inverted hexagonal phase. (Reprinted with the permission of the American Chemical Society [113])...

Cyclic carbohydrates with two alkyl chains (e.g. 1,2-dialkyl (or 1,2-diacyl) glycerol 8 a (sug=Glcp, Galp) present structural similarities with glycerophospho-lipids. They form complex mesophases such as bicontinuous cubic phases, inverted hexagonal phases or myelin figures [58-61]. Other dialkyl derivatives... 

Seddon, J. M. (1990). Structure of the inverted hexagonal (HII) phase, and non-lamellar phase transitions of lipids, Biochim. Biophys. Acta, 1031, 1-69. 

Phospholipid(s) 379, 380,382 - 387, 392. See also Specific substances bilayer diagram 391 head groups, functions of 396 inverted hexagonal phase 397 31P NMR 397 non-bilayer structures 397 Phosphomannomutase 654 Phosphomutases 526 Phosphonamidate 626s... 

Koltover, I., Salditt, T., Radler, J.O. and Safinya, C.R. (1998) An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery. Science, 281, 78-81. 

Figure 10.1 Schematic of two distinct pathways from the lamellar phase to the columnar inverted hexagonal i i phase of cationic liposome/DNA (CL/DNA) complexes. Along Pathway 1 the natural curvature C0=l/Ro of the cationic lipid monolayer is driven negative by the addition of the helper-lipid DOPE. This is shown schematically (middle top) where the cationic li DOT(4P is cylindrically shaped while DOPE is cone-like leading to the negative curvature. Along pathway II the to j transition is induced by the addition of a new class of helper-lipids consisting of mixtures...

THE INVERTED HEXAGONAL PHASE OF CATIONIC LIPOSOM/DNA COMPLEXES PATHWAYS FROM LAMELLAR PHASE... 

Figure 10.7 Synchrotron SAXS patterns of the lamellar and columnar inverted hexagonal Hfi phases of positively charged CL/DNA complexes as => function of increasing weight fraction < DOpe- At 4>dope=0.41, the SAXS results from a single phase with the lamellar La structure sv, m in Figure 10.5. At 4>DOpe=0.7, the SAXS scan results from a single phase with the coN nar inverted h. gonal ui structure shown in Figure 10.9. At 4>DOpe=0.65, the SAXS shows coexistence of the (arrows) and Hjj phases (Adapted from Koltover etal., 1998).

INTERACTIONS BETWEEN LAMELLAR AND INVERTED HEXAGONAL Hn PHASE OF CL/DNA COMPLEXES AND ANIONIC GIANT LIPOSOMES MIMICKING THE CELL PLASMA MEMBRANE... 

Synchrotron SAXS patterns of the lamellar and columnar inverted hexagonal n 180... 

Color Plate 8 Schematic of two distinct pathways from the lamella L phase to the columnar inverted hexagonal Hfi phase of cationic liposome/DNA (CL/DNA) complexes. (see page 192)... 

Fig. 4 Elongation of the R3 phosphate ester chain of the cationic PC results in nonlamellar phase formation. Small-angle X-ray diffraction patterns recorded at 20° C show (a) lamellar La (b) cubic Pn3m (c) inverted hexagonal Hn phases formed by dioleoyl cationic PCs with ethyl, hexyl and octadecyl R3 chains, respectively, diCl8 1 -EPC [19], diC18 l-C6PC [20] and diC18 l-C18PC [21]...

Generally, lipids forming lamellar phase by themselves, form lamellar lipoplexes in most of these cases, lipids forming Hn phase by themselves tend to form Hn phase lipoplexes. Notable exceptions to this rule are the lipids forming cubic phase. Their lipoplexes do not retain the cubic symmetry and form either lamellar or inverted hexagonal phase [20, 24], The lamellar repeat period of the lipoplexes is typically 1.5 nm higher than that of the pure lipid phases, as a result of DNA intercalation between the lipid bilayers. In addition to the sharp lamellar reflections, a low-intensity diffuse peak is also present in the diffraction patterns (Fig. 23a) [81]. This peak has been ascribed to the in-plane positional correlation of the DNA strands arranged between the lipid lamellae [19, 63, 64, 82], Its position is dependent on the lipid-DNA ratio. The presence of DNA between the bilayers has been verified by the electron density profiles of the lipoplexes [16, 62-64] (Fig. 23b). 

Certain cationic lipids were found to form inverted hexagonal phase lipoplexes [21, 46, 85-87]. The Hn phase lipoplexes consist of DNA coated by lipid monolayers and arranged on a two-dimensional hexagonal lattice. This arrangement is identified by small-angle X-ray reflections in the ratio 1 3 4 (Fig. 24a). The lower intensity of the (11) and (20) lipoplex diffraction peaks relative to the Hn pattern... 

Fig. 24 Inverted hexagonal phase lipoplexes with cationic PCs forming HII phase (a) and cubic Pn3m phase (b). Lipid/DNA 4 1 w/w, 37 °C [46] (reproduced by permission of the Royal Society of Chemistry)...

Due to its ability to form inverted hexagonal phase, DOPE is believed to impart fusogenicity to lipoplexes, thus facilitating fusion followed by destabilization of the endosomal membrane, lipoplex escape from the endosomes, and eventually the DNA release. Indeed, inclusion of DOPE into lipoplexes was shown to enhance considerably the transfection activity of some of the cationic lipid carriers [35,120, 121]. For example, formulations of oxypropyl quaternary ammonium cationic lipids with 50 mol% DOPE have been reported to exhibit 2-5 times higher transfection activity in COS7 cells than formulations with pure cationic lipid (Fig. 29) [35]. Recently, a triple-bond dialkynoyl analog of DOPE has been... 

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