title: Amyloids of alpha-synuclein affect the structure and dynamics of supported lipid bilayers.
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.
authors.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.
authors.forename: Aditya
authors.initials: A
authors.lastname: Iyer
authors.affiliation: 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.
authors.forename: Nils O
authors.initials: NO
authors.lastname: Petersen
authors.affiliation: Nanobiophysics Group, MESA+ Institute for Nanotechnology and MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Mireille M A E
authors.initials: MM
authors.lastname: Claessens
authors.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. Electronic address: subramaniam@amolf.nl.
authors.forename: Vinod
authors.initials: V
authors.lastname: Subramaniam
mesh_terms: D000327:Adsorption; D000682:Amyloid / Q000378:metabolism*; D052160:Benzothiazoles; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D050505:Mutant Proteins / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D066329:Protein Aggregates; D011485:Protein Binding; D013194:Staining and Labeling; D013844:Thiazoles / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D000682:Amyloid; D052160:Benzothiazoles; D008051:Lipid Bilayers; D008081:Liposomes; D050505:Mutant Proteins; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D066329:Protein Aggregates; D013844:Thiazoles; D051844:alpha-Synuclein; C009462:thioflavin T; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine