Nonlamellar phases

The structural and dynamical properties of micelles have been investigated by many groups, using different approaches such as continuum models and lattice models - and using atom-atom potentials without s,79 and with explicit solvent molecules. All these models have helped in furthering our understanding of micelle structure and dynamics. 

Watanabe and Klein have reported MD simulations of the hexagonal mesophase of sodium octanoate in water with hexagonal symmetry. The singlet (i.e., one atom) probability distribution functions of the carbon atoms on the hydrocarbon chains show close similarity to those in the micelle. The dynamics of water molecules close to the head groups shows lower mean square displacements, and their orientational correlation function decays more slowly than those of waters farther from the head groups, as was seen in a recent bilayer simulation.6  

---

Veiga, M.P., Arrondon, J.L. Goni, P.M. and Alonso, A., 1999, Ceramides in phospholipid membranes effects on bilayer stability and transition to nonlamellar phases. Biophys. 7. 76 342-350... 

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]...

Even though the individual lipid components form stable lamellar phases, formation of inverted nonlamellar phases in EDOPC mixtures with anionic lipids of the type found in cell membranes is certainly not surprising, taking into account a number of reports which demonstrate that a variety of cationic/anionic lipid... 

Correlation of Transfection Activity with Lamellar-to-Nonlamellar Phase Conversions in Cellular Lipids... 

Given the need for intermixing of membrane lipids with lipoplex lipids as an important step in the sequence of transfection events, a set of recent findings, discussed below, takes on particular significance. These findings demonstrate that transfection efficiency closely correlates both with the cationic PC chain structure (Fig. 13a) [26] and with its effect on the lamellar-to-nonlamellar phase progressions observed in membrane lipids upon mixing with cationic PCs (Fig. 13, 26, and 27). 

The effect of double bonds on both transfection and phase behavior is well illustrated by the pair C18 1/C10-EPC and C18 0/C10-EPC. These two lipids differ by one double bond only. However, the unsaturated lipid is over ten times more efficient as transfection agent than the saturated one [112]. The superior efficiency of C18 1/C10-EPC relative to C18 0/C10-EPC is also implied by the phases that evolve in membrane lipid formulations upon mixing with these two cationic lipids. A biomembrane-mimicking lipid formulation DOPC/DOPE/DOPS/Chol 45 20 20 15 remained lamellar in mixtures with C18 0/C10-EPC in contrast, the more efficient C18 1/C10-EPC induced a lamellar-nonlamellar phase conversion in this mixture, which was taking place at physiological temperature (Fig. 27). 

Cellular anionic lipids have a twofold effect on DNA release from the lipo-plexes. They compensate the cationic lipid surface charge and eliminate the electrostatically driven DNA binding to the membrane interface, and they also disrupt the lipoplex structure and facilitate DNA departure into the solution by inducing formation of nonlamellar phases upon mixing with the lipoplex lipids. 

Tenchov BG, Wang L, Koynova R et al (2008) Modulation of a membrane lipid lamellar-nonlamellar phase transition by cationic lipids a measure for transfection efficiency. Biochim Biophys Acta-Biomembranes 1778 2405-2412... 

Koynova R, MacDonald RC (2007) Natural lipid extracts and biomembrane-mimicking lipid compositions are disposed to form nonlamellar phases, and they release DNA from lipoplexes most efficiently. Biochim Biophys Acta-Biomembranes 1768 2373-2382... 

Lewis RNAH, McElhaney RN (2000) Surface charge markedly attenuates the nonlamellar phase-forming propensities of lipid bilayer membranes calorimetric and P-31-nuclear magnetic resonance studies of mixtures of cationic, anionic, and zwitterionic lipids. Biophys J 79 1455-1464... 

Koynova R, Wang L, MacDonald RC (2006) An intracellular lamellar - nonlamellar phase transition rationalizes the superior performance of some cationic lipid transfection agents. Proc Nad Acad Sci USA 103 14373-14378... 

Several classes of lipids common for the biomembranes can form inverted nonlamellar phases under physiologic conditions (4). The principle ones are phosphatidylethanolamines and monogalactosyldiglycerides. Also, cardiolipins and phos-phatidic acids can form inverted phases in the presence of divalent cations, and phosphatidylserines and phosphatidic acids both form inverted phases at low pH. Moreover, biomembrane lipid extracts and membrane-mimicking lipid compositions form nonlamellar phases if heated above physiologic temperatures, dehydrated, or treated with divalent cations (5-7). 

A biologic reason for the abundance of nonlamellar lipids in membranes is that they possess the ability to modulate the activities of membrane proteins (15, 16). It has been recognized that membranes exist in a state of curvature frustration, which may be sufficiently large to have significant effect on certain protein conformations (17). Many examples show that the lipid bilayer elastic curvature stress indeed couples to conformational changes of membrane proteins (15, 18, 19). Protein kinase C is one such example of an enzyme activated by lipids that exhibit a propensity for nonlamellar phase formation (20). The activity of Ca " -ATPase from sarcoplasmic reticulum membranes also strongly correlates with the occurrence of nonbilayer lipids in the membrane and increases with the increase of their amount. It is noteworthy that the protein activity does not depend on the chemical structure of the lipids but only on their phase propensity thus specific binding interactions are ruled out. The list of proteins with activities that depend on the phase properties... 

Proposed more than 20 years ago, the stalk intermediate—a highly curved lipid stmcture— provides the most plausible description of the initial fusion stage currently available. The related stalk-pore mechanism (23-25) of fusion is viewed favorably by most researchers. It shows the close relation between fusion and the transition from lamellar into bilayer cubic and hexagonal phases (see Fig. 4 in the section entitled Formation of nonlamellar phases in membrane lipids ). Studies on the rhombohedral phase formed in partially dehydrated lipids provide another insight into the possible structure of fusion stalks (26). 

Table 1 Gel — liquid-crystalline and lamellar — nonlamellar phase transition temperatures [°C] of fully hydrated lipids as a function of the lipid polar head group and hydrocarbon chain length (33, 46, 52, 55, 56)...

Lindblom G, Rilfors L. Nonlamellar phases formed by membrane-lipids. Adv. Colloid Interface Sci. 1992 41 101-125. 

---