Tightly packed lipid lamellae with large conformational flexibility in theinterfacial 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 glycoli pids (mostly gangliosides) with bulky and charged headgroups made up of sev eral sugar units. These headgroups have a large conformational flexibility and they are usually assumed to lie roughly parallel or perpendicular to th e membrane surface, in connection with the well-known property of gangliosi des to be involved in signal recognition and transduction. This paper deals with the study of the geometry of an array of planar lipid lamellae, conta ining flexible headgroups, confined in a rigid box and subject only to repu lsive forces of steric and electrostatic origin. Under the assumption of co nstant conformational population of the heads we get, by Euler-Lagrange ene rgy minimization, the expected result of a constant repeat distance dictate d by the solvent-lipid volume ratio. By contrast, when the conformational p opulation 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 conformat ion, the fluctuations of the repeat distance are large and the domains wide r, while in the opposite case of a weak modulation of the repulsion by the headgroup structure, the fluctuation amplitude is negligible and the domain s are small. Although the periodic modulation of the repeat distance looks to be an ubiquitous effect, its magnitude seems to be small for most amphip hiles. However, in the case of flexible and very bulky headgroups, the phen omenon could be relevant. Our model differs from the classical picture of p hase separation arising from the balance between attractive and repulsive ( mixing entropy) forces, because, as suggested by force apparatus measuremen ts, only repulsion energy among ganglioside lamellae is dominant. The model predictions have been confirmed by X-ray measurements in binary water-gang lioside mixtures which clearly show a modulation of the repeat distance in a rather large region of the phase diagram, while only a single repeat dist ance has been so far observed for the more common phospholipids lamellae.