The role of the monosialoganglioside-GM1 in the interaction between model membranes and unstructured metastable amyloid oligomers of salmon calcitonin

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.