title: Formation of lipid/peptide tubules by IAPP and temporin B on supported lipid membranes.
abstract: The conversion of various and to is accelerated by , which are also postulated to represent targets mediating the cytotoxicity of protofibrils. Yet, our understanding of the molecular details governing -catalyzed fibrillogenesis of precursors remains limited. To obtain insight into the intricate interplay of and biophysics we have recently introduced supported bilayers (SLBs) with fluorescent analogs as model biomembranes, observed by time-lapse . Here we demonstrate that human islet () induces within minutes of its application on bilayers the expulsion of numerous flexible tubules from the . Intriguingly, these flexible tubules gradually evolve into a network of straight tubes locally attached to the substrate. Two-color imaging of the and the fluorescently labeled revealed to be distributed along the . Similar linear tubules were observed with the antimicrobial temporin B and the non-amyloidogenic rat , revealing that the above mesoscopic perturbations are not related to formation by the human . Micromanipulation experiments revealed that the linearity of the tubules was caused by tension, stretching the tubules between their points of attachment to the substrate. After longer incubation times, for SLBs containing the oxidatively modified 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (, bearing a terminal carboxyl at the end of the chain) and human (but not the other ) some of the straight transformed into highly regular helices. This is likely to reflect tension originating from an efficient aggregation of the into parallelly aligned bundles, associated with tubes containing the oxidized , possibly together with a concomitant flow of along the tubules to the immobile aggregates attaching the tubules to the substrate, these two processes cause, upon shortening of the linear scaffold, the attached excess tubule to adopt a helical morphology, coiling around the core. The above studies are in line with the multiphasic kinetics of fibrillation in the presence of oxidized containing liposomes, assessed by fluorescence enhancement. In addition to demonstrating the feasibility of SLBs as biomimetic model system for studying -assisted fibrillation, our results accentuate the role of chemical composition in modulation of different stages of this process and the associated transformation of architecture. Accordingly, changes in the chemical nature of cellular arising from pathophysiological processes such as oxidative stress may participate in the triggering amyloidogenesis as well as amplification of its detrimental effects in vivo.
authors.affiliation: Helsinki Biophysics & Biomembrane Group, Medical Biochemistry/Institute of Biomedicine, University of Helsinki, P.O. Box 63 (Haartmaninkatu 8), FIN-00014, Finland. paavo.kinnunen@helsinki.fi.
authors.forename: Paavo K J
authors.initials: PK
authors.lastname: Kinnunen
authors.affiliation: Helsinki Biophysics & Biomembrane Group, Medical Biochemistry/Institute of Biomedicine, University of Helsinki, P.O. Box 63 (Haartmaninkatu 8), FIN-00014, Finland. paavo.kinnunen@helsinki.fi.
authors.forename: Yegor A
authors.initials: YA
authors.lastname: Domanov
authors.affiliation: Helsinki Biophysics & Biomembrane Group, Medical Biochemistry/Institute of Biomedicine, University of Helsinki, P.O. Box 63 (Haartmaninkatu 8), FIN-00014, Finland. paavo.kinnunen@helsinki.fi.
authors.forename: Juha-Pekka
authors.initials: JP
authors.lastname: Mattila
authors.affiliation: Helsinki Biophysics & Biomembrane Group, Medical Biochemistry/Institute of Biomedicine, University of Helsinki, P.O. Box 63 (Haartmaninkatu 8), FIN-00014, Finland. paavo.kinnunen@helsinki.fi.
authors.forename: Teemu
authors.initials: T
authors.lastname: Varis
mesh_terms: D023181:Antimicrobial Cationic Peptides; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: C528536:1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine; D023181:Antimicrobial Cationic Peptides; D005456:Fluorescent Dyes; D058228:Islet Amyloid Polypeptide; D008051:Lipid Bilayers; D008081:Liposomes; D011506:Proteins; C104501:temporin; D010767:Phosphorylcholine