A 3-D Hexagonal Inverse Micellar Lyotropic Phase

Abstract

Lipids are ubiquitous in nature; together with proteins they constitute the plasma membranes of cells, and take part in a plethora of biological processes, ranging from cell signalling 1 and actin assembly 2 through to endo-and exo-cytosis 3 . More recently, lipids and other amphiphiles have been used as vehicles for drug delivery 4 . Understanding lipid polymorphism is the key to understanding biochemical control at membranes and to the development of intracellular delivery systems.When mixed with a polar solvent, amphiphiles self-assemble into fluid interfacial structures where polar headgroups at the interface shield hydrocarbon chains from contact with the solvent. Most biological amphiphiles form 'inverse' liquid-crystalline phases where the interface curves towards the polar region. Conversely, most simple surfactants form 'normal' phases, where the interface bends away from the polar solvent and towards the chain region. Those lipids with a tendency for curvature play important roles in regulating the dynamics and function of membrane proteins, and are essential for enabling lipid based drug/gene delivery systems to fuse with the cell membrane. Those lipids with the greatest tendency for inverse interfacial curvature form spherical structural elements, where a core of water is surrounded by a monolayer of lipid. In some cases such inverse micelles are found to self-assemble into a close packing of cubic symmetry. Although only one such packing, of space group Fd3m, has so far been identified 5 , we have sought to find different inverse micellar packings, of primitive, body-centred or facecentred cubic symmetry, mirroring the more diverse range of normal micellar cubic phases found in surfactant systems 6,7 . Here we report only the second liquid crystalline structure based on a close packing of inverse micelles: a 3-D hexagonal inverse micellar phase, of space group P6 3 /mmc.Seddon et al. 8 previously reported the formation of an Fd3m phase in excess water for a mixture of two typical lipids, dioleoylphosphatidylcholine (DOPC) and dioleoylglycerol (DOG). They also observed a different phase at lower water concentrations, but were unable to give an unambiguous phase determination, although electrical conductivity measurements and freeze-fracture electron microscopy suggested that this phase also consisted of packed inverse micelles. The Fd3m cubic phase was also found in a mixture of egg phosphatidylcholine, egg phosphatidylethanolamine, 1,2-diacylglycerol (derived from egg phosphatidylcholine) and cholesterol, at 1,2-diacylglycerol concentrations in excess of 40 mol% 9 . For the present study, we prepared ternary lipid mixtures comprising DOPC, DOG and cholesterol, of molar ratios 1:2:1 and 1:2:2, in excess water. Small-angle X-ray scattering (SAXS) experiments were carried out at the European Synchrotron Radiation Facility, Grenoble, France. Detailed information regarding the experimental procedure can be found in the Supporting Information.The phase behaviour of both ternary mixtures was found to be v...

Phase Behavior, Functions, and Medical Applications of Soy Phosphatidylcholine and Diglyceride Lipid Compositions

“…The calculated lattice parameters for this 3D hexagonal phase are a = 6.99 and c = 11.35 nm with a c/a ratio of 1.624, which is very close to the value for the ideal hcp lattice of identical spheres, R ideal = ffiffi ffi 8 p :3 = 1.633. In addition, the intensities of obtained SAXS reflections are similar to those obtained for the 3D hexagonal P6 3 /mmc phase of other lipid 15 and surfactant 16 systems in water.…”

Pressure effects on lipid membrane structure and dynamics

“…These can form as either type I, oil in water or type II water in oil structures, indicated by subscript I or II respectively. These structures include the biologically ubiquitous flat fluid lamellar (L ␣ ) phase, 2-dimensional hexagonal phases (H I , H II ), bicontinuous cubic phases (Q I , Q II ) and micellar cubic phases (including a recently discovered (Shearman et al, 2009) type II micellar 3-D hexagonal phase).The structure adopted by a particular lipid system depends strongly on the lipids' preferred curvature, as well as more subtle effects such as chain packing frustration . All of these factors can be affected by pressure .…”

Ordered micellar and inverse micellar lyotropic phases

“…The packing of the ordered micellar phases: (a) Pm3n, (b) Fm3m, (c) Im3m, (d) Fd3m, (e) P6 3 /mmc. The first three (taken, with permission, from Sakya et al [32]) are Type I structures, whereas the latter two are shown as Type II, inverse micellar phases (taken, with permission, from Seddon et al [16] and Shearman et al [26], respectively).…”