Transduction to self-assembly of molecular geometry and local interactions in mixtures of ceramides and ganglioside GM1

Abstract

In mixed monolayers with ganglioside GM1, ceramide induces a non-ideal increase of the monolayer collapse pressure, a reduction of the mean molecular area and a decrease of the surface potential per molecule at all surface pressures. The critical packing parameter and van der Waals interaction energy calculated from monolayer data predict the transduction of changes from the molecular to the supramolecular level, such as formation of bilayers and possible subsequent facilitation of non-bilayer structures as the ceramide concentration increases, along with a greater thermal stability of the lipid structures. In agreement with the expectations from monolayer data, calorimetry, dynamic light scattering and electron microscopy data reveal the actual presence of phases with high phase-transition temperatures; at about 5 mol% ceramide in the mixture, the aggregates change their topology from micelles to multilamellar vesicles of increasing size and finally to long, thin tubules as the amount of ceramide in the system increases.

The many faces (and phases) of ceramide and sphingomyelin II – binary mixtures

“…The SM/Cer mixtures were characterized by area condensation at low surface pressures and film stiffening at high surface pressures, indicating not only attractive interactions but also complementary accommodation of the molecules at the interface (Dupuy and Maggio 2014). Similar packing interactions were observed in binary mixtures in which one of the components bears a smaller polar head group than the other, such as in the Bmolecular cavity^effects in mixed films of GM1/Cer (Carrer and Maggio 2001;Maggio 2004) and GM1/dipalmitoyl-PC (Frey et al 2008).…”

“…7c) with ideal behavior of the surface potential/molecule. This suggests a Bmolecular cavity^effect (Maggio et al 1997;Carrer and Maggio 2001;Diociaiuti et al 2004), consistent with reduction of the mean molecular area with essentially unchanged dipolar properties of the lipids and of the film elasticity compared to an ideally mixed film. The interactions of Cer with ganglioside GD3, located at a further diversion point in the biosynthetic pathway of complex gangliosides (Maccioni et al 2002;Yu et al 2004), are similar to those of mixtures with GM3 (Fig.…”

“…The variation of mean molecular area and average surface potential/molecule, with respect to the ideal behavior, in a binary monolayer can be due to changes of the molecular parameters of one, the other, or both lipid components (Maggio et al 1997;Carrer and Maggio 2001). At constant (low or high) surface pressure, the contribution of Cer to the cross-sectional molecular area and surface potential/molecule in mixed monolayer with GlcCer at high proportions of Cer do not show large changes compared to the area contribution in pure Cer films (Fig.…”

“…On the other hand, in films with increasing proportions of ganglioside, the Cer contribution to the mean molecular area of the mixture is, at first, greatly reduced and then it no longer contributes to the film area and its partial molecular area can even acquire negative values (Maggio 2004). This indicates that Cer becomes Bsequestered^in surface defects due to irregular lateral packing in the two-dimensional ganglioside-enriched lattice (Carrer and Maggio 2001;Rosetti et al 2003;Maggio 2004). The films are non-ideal, exhibiting strong condensation and depolarization that reveals molecular interactions and Bmiscibility^on the nm scale range according to the additivity rule.…”

“…For example, at the local nm level, molecular immiscibility (or ideal full miscibility) in binary monolayers (with or without macroscopic phase domain separation on the μm scale range) can be inferred by the existence of smooth surface pressure-area isotherms, linear additive variation of mean molecular area, and dipole potential density as a function of the film composition, together with composition-invariant collapse pressures (Phillips 1972;Brockman 1994;Maggio et al 1997;Carrer and Maggio 2001;Maggio 2004). In binary or ternary systems, lateral immiscibility can be visually observed on the μm scale range by the presence of segregated phase or compositional domains (McConnell 1990;Möhwald 1995;Maggio 2000, 2002;Fanani et al 2002;Rosetti et al 2003).…”