Gangliosides and the multiscale modulation of membrane structure

► In this review, we focused on the importance of ganglioside molecular complexity in determining the overall complexity of membranes and membrane structure. ► We addressed the importance of gangliosides in modulating: Membrane curvature and geometric properties, membrane two-dimensional and transverse structure, lipid–protein interactions. ► In addition, we discussed the relevance of ganglioside–cholesterol pair in determining membrane structure. Cellular membranes are highly organized structures with multiple and multi-dimensional levels of order where lipid components are active players. The lipid role is especially evident in rafts, where lipid-driven collective interaction dictates the local structure of a membrane. However, lipids play as well other roles in many aspects of membrane mechanics and function. In this review, we would like to re-focus the attention of the readers on the importance of gangliosides in organizing the fine structure of cellular membranes, in lateral and transverse directions. Important biological events are likely to be affected such as the dynamic control of the shape of specialized plasma membrane areas and of the intracellular organelles, the in- and outward budding and fusion of membrane vesicles, the physical and functional coupling of the outer and the inner plasma membrane leaflet, involved in the transduction of signals across the membrane.