Amyloids of Alpha-Synuclein Affect the Structure and Dynamics of Supported Lipid Bilayers |
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| Authors: | Aditya Iyer Nils?O. Petersen Mireille?M.A.E. Claessens Vinod Subramaniam |
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| Affiliation: | †Nanoscale Biophysics Group, FOM Institute AMOLF, Amsterdam, The Netherlands;‡Nanobiophysics Group, MESA+ Institute for Nanotechnology and MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands;§Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada |
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| Abstract: | 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. |
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