Phase lamellar/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.)... 

Seddon, J.M., Cevc, G., and Marsh, D. (1983) Calorimetric studies of the gel-fluid transition (Lj) —> La) and lamellar-inverted hexagonal (La — H ) phase transition in dialkyl- and diacyl-phosphatidylethanolamines. Biochemistry 22 1280-1289. 

Dispersions of double-chain nonlamellar membrane Mpids most frequently display a lamellar-inverted hexagonal, L -Hw, phase... 

Seddon JM, Cevc G, Marsh D. Calorimetric studies of the gel-fluid (L-Beta-L-Alpha) and lamellar-inverted hexagonal (L-Alpha-HB) phase-transitions in dialkyl and diacylphosphatidylethanolamines. Biochemistry 1983 22 1280-1289. 

Figure 4.2 Lipid phases, (a) Gel (Lp) lamellar phase, (b) Liquid-crystalline Lj) or fluid lamellar phase, (c) Inverted hexagonal (Hn) phase, (d) Hexagonal phase. [Reproduced from R.B. Gennis (1989) Biomernbranes Molecular Structure and Function. Springer New York, (p. 41), with permission]...

M. Caflfey, Kinetics and mechanism of the lamellar gel lamellar liquid-crystal and lamellar inverted hexagonal phase-transition in phosphatidylethanolamine a real x-ray diffraction... 

Siegel, D.P. (1999) The modified stalk mechanism of lamellar/inverted hexagonal phase transitions and its implications for membrane fusion. Biophysical Journal, 76, 291-313. 

The major lyotropic phases encountered with double-chain phospholipids are lamellar, inverted hexagonal, and cubic phases. Single chain lipids have surfactant properties and can also fonn spherical and cylindrical micelles. Figure 5 shows some of the possible aggregation stnictures. Phospholipids not only show lyotropic mesomorphism, i. e. different phases as a ftmetion of water content, but also thennotropic mesomorphism, i. e. transitions between different phases can be induced by varying the temperature. 

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

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... 

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). 

Siegel DP, Epand RM (1997) The mechanism of lamellar-to-inverted hexagonal phase transitions in phosphatidylethanolamine implications for membrane fusion mechanisms. Biophys J 73 3089-3111... 

CL-DNA complexes form spontaneously when solutions of cationic liposomes (typically containing both a cationic lipid and a neutral helper lipid) are combined. We have discovered several distinct nanoscale structures of CL-DNA complexes by synchrotron X-ray diffraction, three of which are schematically shown in Fig. 1. These are the prevalent lamellar phase with DNA sandwiched between cationic membranes (Lo,c) [22], the inverted hexagonal phase with DNA encapsulated within inverse lipid tubes (Hnc) [23], and the more recently discovered Hj0 phase with hexagonally arranged rod-like micelles surrounded by DNA chains forming a continuous substructure with honeycomb symmetry [24]. Both the neutral lipid and the cationic lipid can drive the formation of specific structures of CL-DNA complexes. The inverse cone shape of DOPE favors formation of the... 

For lamellar CL-DNA complexes, endosomal escape via activated fusion limits TE and strongly depends on aM, whereas the inverted hexagonal phase promotes... 

As stated, biological membranes are normally arranged as bilayers. It has, however, been observed that some lipid components of biological membranes spontaneously form non-lamellar phases, including the inverted hexagonal form (Figure 1.9) and cubic phases [101]. The tendency to form such non-lamellar phases is influenced by the type of phospholipid as well as by inserted proteins and peptides. An example of this is the formation of non-lamellar inverted phases by the polypeptide antibiotic Nisin in unsaturated phosphatidylethanolamines [102]. Non-lamellar inverted phase formation can affect the stability of membranes, pore formation, and fusion processes. So-called lipid polymorphism and protein-lipid interactions have been discussed in detail by Epand [103]. 

Siegel, D. P. (1986), Inverted micellar intermediates and the transitions between lamellar, cubic, and inverted hexagonal lipid phases. II. Implications for membrane-membrane interactions and membrane fusion, Biophys. J., 49(6), 1171-1183. 

Figure 2. Ternary phase diagram of the system didodecyldimethylammonium bromide / water / hexene at 25°C. The nomenclature is cub cubic phase Lamj and Lam2 lamellar phases l.c. liquid crystalline, inverted hexagonal phase L2 microemulsion phase, with curvature toward water. (Courtesy of K. Fontell).

The propensity of membranes to fuse correlates with the fraction of inverted phase-forming lipids conversely, membrane fusability is reduced with an increase of the lipid fraction that inhibits inverted phase formation. Substantial evidence suggests that the mechanism of lipid membrane fusion is related to the mechanism of lamellar/inverted phase transitions (23). The intermediates that form in membrane fusion seem to be identical to those that form during the transformations between lamellar, bicontinuous inverted cubic and inverted hexagonal lipid liquid-crystalline phases, and these transitions can be used successfully as a model for studying the lipid membrane fusion mechanism and kinetics. 

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