Figure 3.

Formation of toxic Aβ oligomers can be differently influenced by different local GM₁ organization. Proposed model: (a) and (b) depict the inhibitory effect of low concentrations of GM₁, organized in low-density and dynamic nanoclusters, on the membrane-mediated oligomerization of Aβ (membrane-bound peptide is symbolized by the yellow arrows). (a) Membrane-mediated oligomerization of low nanomolar solution concentrations of Aβ (Aβ/total lipid ratios of 1:4000, at maximum) is triggered by the presence of sphingomyelin (green lipids; print version: light gray) (25). (b) Binding of Aβ to the headgroup of GM₁ (red ellipses) sequesters the peptide and prevents it from oligomerizing (25). (c) High concentrations of GM₁, organized in high-density platforms of slow dynamics, create a surface that facilitates the adsorption and local concentration of Aβ. At high Aβ densities, oligomerization of the peptide is promoted (42, 43), which is a generic effect also observed for other surfaces (54, 55). Thus, in the low GM₁ concentration regime (also low local Aβ concentration) the ganglioside acts as an inhibitor of membrane-mediated oligomerization. In the high GM₁ concentration regime—where the membrane is covered by GM₁ (21)—the ganglioside can become a catalyst of oligomerization, depending on the amount of Aβ on the surface of the GM₁ platform. To see this figure in color, go online.