To investigate the molecular mechanisms of the interaction between amyloid aggregates and model
membranes containing GM1, we applied Circular Dichroism (CD) spectroscopy and Transmission Electron
Microscopy (TEM). In particular, we studied the interaction of sCT monomers, prefibrillar oligomers (PFOs), proto- and mature-fibers with liposomes made of DPPC, with and without GM1 and cholesterol. All data
indicated that the presence of the negatively charged GM1 favored the interaction with all types of aggrega
accelerating the formation of beta-structures. TEM data clearly showed that only PFOs were able to modify the
bilayer structures by the formation of “amyloid channels” that were clearly visualized. Their structure was very similar to that proposed by Molecular Dynamics simulations for Abeta. CD data are compatible with this hypothesis. We speculate that the electrostatic interaction occurring between positively charged, native, flexible PFOs with the negatively charged GM1 localized in the outer part of the lipid bilayer, drives the initial binding while the hydrophobic interaction could be responsible for the subsequent incorporation in the membrane leading to the formation of the observed amyloid pores
