Interactions of monomeric alpha-synuclein (αS) with lipid membranes have been suggested to play an important role in initiating aggregation of αS. We have systematically analyzed the distribution and self-assembly of monomeric αS on supported lipid bilayers. We observe that at protein/lipid ratios higher than 1:10, αS forms micrometer-sized clusters, leading to observable membrane defects and decrease in lateral diffusion of both lipids and proteins. An αS deletion mutant lacking amino-acid residues 71–82 binds to membranes, but does not observably affect membrane integrity. Although this deletion mutant cannot form amyloid, significant amyloid formation is observed in the wild-type αS clusters. These results suggest that the process of amyloid formation, rather than binding of αS on membranes, is crucial in compromising membrane integrity.

Additional Metadata
Publisher Elsevier/ Cell Press
Persistent URL dx.doi.org/10.1016/j.bpj.2014.05.001
Journal Biophys. J.
Citation
Iyer, A, Petersen, N. O, Claessens, M. M. A. E, & Subramaniam, V. (2014). Amyloids of Alpha-Synuclein Affect the Structure and Dynamics of Supported Lipid Bilayers. Biophys. J., 106(12), 2585–2594. doi:10.1016/j.bpj.2014.05.001