title: Atomic force microscopy reveals defects within mica supported lipid bilayers induced by the amyloidogenic human amylin peptide.
abstract: To date, over 20 peptides or proteins have been identified that can form amyloid fibrils in the body and are thought to cause disease. The mechanism by which amyloid peptides cause the cytotoxicity observed and disease is not understood. However, one of the major hypotheses is that amyloid peptides cause membrane perturbation. Hence, we have studied the interaction between lipid bilayers and the 37 amino acid residue polypeptide amylin, which is the primary constituent of the pancreatic amyloid associated with type 2 diabetes. Using a dye release assay we confirmed that the amyloidogenic human amylin peptide causes membrane disruption; however, time-lapse atomic force microscopy revealed that this did not occur by the formation of defined pores. On the contrary, the peptide induced the formation of small defects spreading over the lipid surface. We also found that rat amylin, which has 84% identity with human amylin but cannot form amyloid fibrils, could also induce similar lesions to supported lipid bilayers. The effect, however, for rat amylin but not human amylin, was inhibited under high ionic conditions. These data provide an alternative theory to pore formation, and how amyloid peptides may cause membrane disruption and possibly cytotoxicity.
authors.affiliation: M.E. Müller Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
authors.forename: J D
authors.initials: JD
authors.lastname: Green
authors.forename: L
authors.initials: L
authors.lastname: Kreplak
authors.forename: C
authors.initials: C
authors.lastname: Goldsbury
authors.forename: X
authors.initials: X
authors.lastname: Li Blatter
authors.forename: M
authors.initials: M
authors.lastname: Stolz
authors.forename: G S
authors.initials: GS
authors.lastname: Cooper
authors.forename: A
authors.initials: A
authors.lastname: Seelig
authors.forename: J
authors.initials: J
authors.lastname: Kistler
authors.forename: U
authors.initials: U
authors.lastname: Aebi
mesh_terms: D000538:Aluminum Silicates; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D003902:Detergents; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D008854:Microscopy, Electron; D008954:Models, Biological; D008969:Molecular Sequence Data; D017830:Octoxynol; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000538:Aluminum Silicates; D000682:Amyloid; D016229:Amyloid beta-Peptides; D003902:Detergents; D058228:Islet Amyloid Polypeptide; D008051:Lipid Bilayers; D011994:Recombinant Proteins; D017830:Octoxynol; C011934:mica