Cubic phase, lipid structure

Luzzati V, Tardieu A, Gulik-Krzywicki T, Rivas E and Reiss-Flusson F 1968 Structure of the cubic phases of lipid-water systems Nature 220 485-8... 

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.)... 

Polar lipids form different kinds of aggregates in water, which in turn give rise to several phases, such as micellar and liquid crystalline phases. Among the latter, the lamellar phase (La) has received the far greatest attention from a pharmaceutical point of view. The lamellar phase is the origin of liposomes and helps in stabilizing oil-in-water (O/W) emulsions. The lamellar structure has also been utilized in creams. We have focused our interest on another type of liquid crystalline phase - the cubic phase... 

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... 

Lindblom, G. and Rilfors, L. (1989). Cubic phases and isotropic structures formed by membrane lipids - possible biological relevance. Biochem. Biophys. Acta, 988, 221-56. 

Mariani, R, Luzzati, V., and Delacroix, H. (1988). Cubic phases of lipid-containing systems structure analysis and biological implications. J. Mol. Biol, 204, 165-89. Marks-Tarlow, T., Robertson, R., and Combs, A. (2001). Varela and the Uroborus the psychological significance of reentry. Cybernetics Human Knowing, 9, 31. 

Pebay-Peyroula, E., Rummel, G., Rosenbusch, IP. and Landau E.M. X-ray structure of bacteri-orhodopsin at 2.5 angstroms from microcrystals grown in lipidic cubic phases (1997) Science 277, 1676-1681... 

Figure 6. Cubic structures in lipid-water systems based on space-filling polyhedra. The data from the monoglyceride-water cubic phases fit with the body-centered structure to the right.

This behavior of the DPoPE/cationic PC mixtures is not surprising, because both the double bonds and hydrocarbon chain length variations are known to have considerable effect on the lamellar-to-nonlamellar transitions in lipids [113]. A specific structural characteristic of lipid arrays that exhibits distinct change around the chain length of 14 carbons is the formation of inverted bicontinuous cubic phases Qn. The latter phases tend to form in diacyl or dialkyl phospholipids... 

FIGURE 2.5 The stacked bilayers of the skin barrier are envisioned as composed of crystalline domains separated by fringes of lipids in the liquid crystalline state.38 The fringe zones may actually oscillate in a very small time scale between a liquid crystalline state and a crystalline (gel) state. Such a tentative idea would mean that the barrier is open just temporarily at a certain location since penetration must occur in the liquid crystalline areas. Thus, the action of a penetration enhancer would be to stabilize a liquid crystalline state or transform it into another type of structure, for example, a cubic phase. 

FIGURE 4.2 Schematic illustration of 2 x 2 x 2 unit cells of a lipid/water phase with gyroid cubic symmetry. In reversed bicontinuous cubic phases the lipid bilayer membrane separates two intertwined water-filled subvolumes resembling 3D arrays of interconnected tunnels. Black box (right) represents an enlargement of a part of the folded liquid crystalline lipid bilayer membrane structure. 

The lipidic cubic phase has recently been demonstrated as a new system in which to crystallize membrane proteins [143, 144], and several examples [143, 145, 146] have been reported. The molecular mechanism for such crystallization is not yet clear, but the interfacial water and transport are believed to play an important role in nucleation and crystal growth [146, 147], Using a related model system of reverse micelles, drastic differences in water behavior were observed both experimentally [112, 127, 128, 133-135] and theoretically [117, 148, 149]. In contrast to the ultrafast motions of bulk water that occurs in less than several picoseconds, significantly slower water dynamics were observed in hundreds of picoseconds, which indicates a well-ordered water structure in these confinements. 

Lipid cubic (51) and sponge (52) phases, as well as bicelles (53), are alternatives to detergents that have been applied successfully to membrane protein crystallization. In these instances, the protein is embedded in a lipid bilayer environment, which is considered more natural compared with the detergents that form micellar phases. In the recent high-resolution crystal structure of the human 32 adrenergic G-protein-coupled receptor, lipid cubic phase was used with necessary cholesterol and 1,4-butandiol additives (54). The cholesterol and lipid molecules were important in facilitating protein-protein contacts in the crystal. 

A central issue in the field of surfactant self-assembly is the structure of the liquid crystalline mesophases denoted bicontinuous cubic, and "intermediate" phases (i.e. rhombohedral, monoclinic and tetragonal phases). Cubic phases were detected by Luzzati et al. and Fontell in the 1960 s, although they were believed to be rare in comparison with the classical lamellar, hexagonal and micellar mesophases. It is now clear that these phases are ubiquitous in surfactant and Upid systems. Further, a number of cubic phases can occur within the same system, as the temperature or concentration is varied. Luzzati s group also discovered a number of crystalline mesophases in soaps and lipids, of tetragonal and rhombohedral symmetries (the so-called "T" and "R" phases). More recently, Tiddy et al. have detected systematic replacement of cubic mesophases by "intermediate" T and R phases as the surfactant architecture is varied [22-24]. The most detailed mesophase study to date has revealed the presence of monoclinic. 

The emerging intuition of mesostructures, discussed in detail in the preceding chapter, implies that many structures, formerly considered to consist of planar sheets, can be very much more complicated, e.g. "mesh" structures. True membrane lipids oiily exhibit phases that share a common feature with the infinite lipid bilayer. The average curvature is zero in the centre of the bilayer. These phases are La (infinite planes), Hn (self-intersecting lamellae) and the alternative cubic phases. 

Cubic lipid phases have a very much more complex architecture than lamellar and hexagonal phases. Their structural characteristics have been elucidated only very recently, and it has become clear that their subtleties are the key to a variety of biological problems. We will consider those subtleties in some detail. The three fundamental cubic minimal surfaces - the P-surface, the D-surface and the gyroid (or G-surface), introduced in Chapter 1, can all be foimd in cubic lipid-water phases. The lipid bilayer is centred on the surface with the polar heads pointing outwards. Water fills the labyrinth systems on each side of the surface. These cubic phases will be termed Cp, CD and CG/ respectively. It is likely that there are other more complex IPMS morphologies in cubic phases of lipid-water mixtures, as yet uncharacterised. 

The minimal surface description naturally reveals the infinite lipid bilayer nature of cubic phases, viz. the fact that a single bilayer with no selfintersections can separate two continuous water regions. If we consider models of these cubic lipid-water phases, the structures of the Cp (or Cd) phases look like water globules separated by bilayers and fused in four (or three) lateral directions, respectively. Such a structure is not consistent with the earlier rod description. 

---