title: Membrane interactions and fibrillization of α-synuclein play an essential role in membrane disruption.
abstract: We studied α-synuclein (αS) aggregation in giant vesicles, and observed dramatic membrane disintegration, as well as lipid incorporation into micrometer-sized suprafibrillar aggregates. In the presence of dye-filled vesicles, dye leakage and fibrillization happen concurrently. However, growing fibrils do not impair the integrity of phospholipid vesicles that have a low affinity for αS. Seeding αS aggregation accelerates dye leakage, indicating that oligomeric species are not required to explain the observed effect. The evolving picture suggests that fibrils that appear in solution bind membranes and recruit membrane-bound monomers, resulting in lipid extraction, membrane destabilization and the formation of lipid-containing suprafibrillar aggregates.
authors.affiliation: Nanobiophysics Group, MESA+ Institute for Nanotechnology, Department of Science and Technology, University Twente, 7500 AE Enschede, The Netherlands.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Chaudhary
authors.forename: Anja N D
authors.initials: AN
authors.lastname: Stefanovic
authors.forename: Vinod
authors.initials: V
authors.lastname: Subramaniam
authors.forename: Mireille M A E
authors.initials: MM
authors.lastname: Claessens
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D066263:Protein Aggregation, Pathological / Q000378:metabolism* / Q000473:pathology*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D051844:alpha-Synuclein