Cubic Phases of Lipid-containing Systems: Elements of a Theory and Biological Connotations

Abstract

It has recently been shown that the structure of two of the six cubic phases so far identified in lipid-containing systems is micellar, one (Q223) of type I, the other (Q227) of type II. The micelles of both phases belong to two distinct classes, those of each class being centred at one of the special positions of the space group. From the chemical viewpoint, phase Q227 seems to require a heterogenous mixture of water-miscible and water-immiscible lipids, whereas phase Q223 has been observed with chemically pure lipids. Also, the area/volume ratio measured at the polar/apolar interface takes the same value in the two types of micelles of phase Q223, different values in those phase Q227, in keeping with the notion that the area/molecule ratio is closely related to the chemical activity of the lipid components. The topological properties of the micellar phases are profoundly different from those of the bicontinuous phases. The bicontinuous cubic phases (Q230, Q224, Q229) are often presented as paradigms of the infinite periodic minimal surfaces (IPMS). Some authors have generalized that notion and sought in the IPMS a unified theory underlying the entire field of lipid polymorphism. These analogies entertain some confusion between the mathematical concept of surface and the physical notion of interface. A few electron density maps are presented to document the distance that separates the polar/apolar interfaces from the IPMS. The maps also show that some of the geometric singularities (points, lines, surfaces) of the structures coincide with the locus of the CH3, ends of the chains and with the very centre of the water matrix, i.e. with the regions where the short-range disorder is highest. We introduce the expression chaotic zones to designate these regions. In all the lipid phases the chaotic zones are found to occupy special geometric positions, either related to the symmetry elements or to the IPMS. It thus appears that it is energetically more advantageous to adopt an orderly disposal of the disposal of the short-range disorder than to minimize the area of the polar/apolar interfaces. Finally, regarding the possible biological significance of lipid polymorphism, the point is stressed that among the phases that are observed in equilibrium with excess water (these phases are also the most likely candidates for a biological role) those with a cubic symmetry deserve special attention. We have previously involved one of the bicontinuous phases (Q224) in speculations regarding the digestion of fats and the structure of the outer membrane of thermoacidophilic archaebacteria. One of the micellar cubic phases (Q227) is also interesting: on the one hand, its chemical composition is related to the enzymatic degradations that lipids may undergo in biological membranes; its physical structure, on the other hand, makes that phase impervious to water. Since the structure of phase Q224 is closely related to that of phase Q227, a "patch-the-puncture" process can be imagined whereby an enzymatic attack of the lipid, leading potentially to a leak in the membrane, might also induce a local transition to a water-tight structure, eventually stopping the leak. That process could play a role in a variety of circumstances of biological interest.