Tightly packed lipid lamellae with large conformational flexibility in the interfacial region may exhibit multiple periodicity in their repeat distance. A theoretical analysis and X-ray verification

The lipid membranes of the nervous system contain a large amount of glycolipids (mostly gangliosides) with bulky and charged headgroups made up of several sugar units. These headgroups have a large conformational flexibility and they are usually assumed to lie roughly parallel or perpendicular to the membrane surface, in connection with the well-known property of gangliosides to be involved in signal recognition and transduction. This paper deals with the study of the geometry of an array of planar lipid lamellae, containing flexible headgroups, confined in a rigid box and subject only to repulsive forces of steric and electrostatic origin. Under the assumption of constant conformational population of the heads we get, by Euler-Lagrange energy minimization, the expected result of a constant repeat distance dictated by the solvent-lipid volume ratio. By contrast, when the conformational population of the heads is allowed to vary in order to reduce the repulsion among the lamellae, the balance between repulsion and conformational energy makes the regular packing unstable, giving rise to periodic modulation of the repeat distance, with alternating domains of loosely and densely packed lamellae. In the case of strong dependence of the repulsion upon conformation, the fluctuations of the repeat distance are large and the domains wider, while in the opposite case of a weak modulation of the repulsion by the headgroup structure, the fluctuation amplitude is negligible and the domains are small. Although the periodic modulation of the repeat distance looks to be an ubiquitous effect, its magnitude seems to be small for most amphiphiles. However, in the case of flexible and very bulky headgroups, the phenomenon could be relevant. Our model differs from the classical picture of phase separation arising from the balance between attractive and repulsive (mixing entropy) forces, because, as suggested by force apparatus measurements, only repulsion energy among ganglioside lamellae is dominant. The model predictions have been confirmed by X-ray measurements in binary water-ganglioside mixtures which clearly show a modulation of the repeat distance in a rather large region of the phase diagram, while only a single repeat distance has been so far observed for the more common phospholipids lamellae.