Single particle tracking to study the binding of protein misfolded oligomer to membrane ganglioside GM1

Recent results suggest an important role of ordered lipid domains of plasma membranes in amyloid aggregation process and its pathogenic effect. We investigated the contribution to toxicity of the membrane ganglioside GM1 in SH-SY5Y neuroblastoma cells exposed to oligomeric conformers of Ab42 and HypF-N endowed with different ultrastructural properties. By means of real-time single particle tracking, we show that misfolded oligomers bind GM1, decreasing its lateral diffusion on the plasma membrane of living cells. In turn, the biochemical response to the oligomeric species results from the membrane content of GM1 and its clustering. Overall, our results indicate an altered membrane raft mobility and clustering in neurons experiencing aberrant protein oligomers.