title: Dynamics of the formation of a hydrogel by a pathogenic amyloid peptide: islet amyloid polypeptide.
abstract: Many chronic degenerative diseases result from aggregation of misfolded polypeptides to form amyloids. Many amyloidogenic polypeptides are surfactants and their assembly can be catalysed by hydrophobic-hydrophilic interfaces (an air-water interface in-vitro or membranes in-vivo). We recently demonstrated the specificity of surface-induced amyloidogenesis but the mechanisms of amyloidogenesis and more specifically of adsorption at hydrophobic-hydrophilic interfaces remain poorly understood. Thus, it is critical to determine how amyloidogenic polypeptides behave at interfaces. Here we used surface tensiometry, rheology and electron microscopy to demonstrate the complex dynamics of gelation by full-length human islet amyloid polypeptide (involved in type II diabetes) both in the bulk solution and at hydrophobic-hydrophilic interfaces (air-water interface and phospholipids). We show that the hydrogel consists of a 3D supramolecular network of fibrils. We also assessed the role of solvation and dissected the evolution over time of the assembly processes. Amyloid gelation could have important pathological consequences for membrane integrity and cellular functions.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Létitia
authors.initials: L
authors.lastname: Jean
authors.affiliation: Department of Bioengineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Chiu Fan
authors.initials: CF
authors.lastname: Lee
authors.affiliation: TA Instruments, Elstree WD6 3SZ, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Hodder
authors.affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Hawkins
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Vaux
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D017666:Deuterium Oxide / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D058228:Islet Amyloid Polypeptide / Q000737:chemistry* / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008854:Microscopy, Electron; D012212:Rheology; D013500:Surface Tension; D014867:Water / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D020100:Hydrogels; D058228:Islet Amyloid Polypeptide; D008081:Liposomes; D014867:Water; D017666:Deuterium Oxide