SMALL CONCENTRATIONS OF ALAMETHICIN INDUCE A CUBIC PHASE IN BULK PHOSPHATIDYLETHANOLAMINE MIXTURES

Under normal conditions, excess water dispersions of liquid crystallin e 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE) are known to convert from a liquid crystalline lamellar (L(alpha)) to inverse hexag onal (H-II) phase at about 60 degrees C. The nonlamellar phase behavio r of lipid systems is also known to depend on the monolayer spontaneou s curvature. The single-channel activity of alamethicin in black lipid bilayer membranes has been shown to be dependent upon the lipid compo sition of the membrane. Since the monolayer spontaneous curvature prop erties (e.g., the monolayer spontaneous curvature, curvature coefficie nts and bilayer thickness) vary with lipid composition, the single-cha nnel activity of alamethicin presumably also correlates with the monol ayer spontaneous curvature properties, Accordingly, we reasoned that i f alamethicin couples to the curvature properties of a lipid film, the n the curvature properties must, in turn, be perturbed by the presence of alamethicin and that this perturbation should be observable in the lipid phase behavior. Here X-ray diffraction and NMR are used to show that the presence of as little as 1% alamethicin introduces a large r egion of cubic phase into the thermal phase diagram. This suggests tha t perturbation of the nonlamellar phase behavior of a lipid system may be a method to survey different channel-forming molecules for possibl e behavior that indicates that the ion channel is sensitive to the mon olayer spontaneous curvature properties.