title: Islet amyloid polypeptide forms rigid lipid-protein amyloid fibrils on supported phospholipid bilayers.
abstract: Islet amyloid polypeptide (IAPP) forms fibrillar amyloid deposits in the pancreatic islets of Langerhans of patients with type 2 diabetes mellitus, and its misfolding and aggregation are thought to contribute to beta-cell death. Increasing evidence suggests that IAPP fibrillization is strongly influenced by lipid membranes and, vice versa, that the membrane architecture and integrity are severely affected by amyloid growth. Here, we report direct fluorescence microscopic observations of the morphological transformations accompanying IAPP fibrillization on the surface of supported lipid membranes. Within minutes of application in submicromolar concentrations, IAPP caused extensive remodeling of the membrane including formation of defects, vesiculation, and tubulation. The effects of IAPP concentration, ionic strength, and the presence of amyloid seeds on the bilayer perturbation and peptide aggregation were examined. Growth of amyloid fibrils was visualized using fluorescently labeled IAPP or thioflavin T staining. Two-color imaging of the peptide and membranes revealed that the fibrils were initially composed of the peptide only, and vesiculation occurred in the points where growing fibers touched the lipid membrane. Interestingly, after 2-5 h of incubation, IAPP fibers became "wrapped" by lipid membranes derived from the supported membrane. Progressive increase in molecular-level association between amyloid and membranes in the maturing fibers was confirmed by Förster resonance energy transfer spectroscopy.
authors.affiliation: Helsinki Biophysics and Biomembrane Group, Medical Biochemistry/Institute of Biomedicine, P.O. Box 63 (Haartmaninkatu 8), FIN-00014 University of Helsinki, Finland.
authors.forename: Yegor A
authors.initials: YA
authors.lastname: Domanov
authors.forename: Paavo K J
authors.initials: PK
authors.lastname: Kinnunen
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010743:Phospholipids
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D008051:Lipid Bilayers; D010743:Phospholipids