Line Activity of Ganglioside GM1 Regulates the Raft Size Distribution in a Cholesterol-Dependent Manner

Liquid-ordered lipid domains, also called rafts, are assumed to be important players in different cellular processes, mainly signal transduction and membrane trafficking. They are thicker than the disordered part of the membrane and are thought to form to compensate for the hydrophobic mismatch between transmembrane proteins and the lipid environment. Despite the existence of such structures in vivo still being an open question, they are observed in model systems of multicomponent lipid bilayers. Moreover, the predictions obtained from model experiments allow the explanation of different physiological processes possibly involving rafts. Here we present the results of the study of the regulation of raft size distribution by ganglioside GM1. Combining atomic force microscopy with theoretical considerations based on the theory of membrane elasticity, we predict that this glycolipid should change the line tension of raft boundaries in two different ways, mainly depending on the cholesterol content. These results explain the shedding of gangliosides from the surface of tumor cells and the following ganglioside-induced apoptosis of T-lymphocytes in a raft-dependent manner. Moreover, the generality of the model allows the prediction of the line activity of different membrane components based on their molecular geometry.