title: Effect of lipid type on the binding of lipid vesicles to islet amyloid polypeptide amyloid fibrils.
abstract: Amyloid deposits, composed primarily of the 37-residue islet amyloid polypeptide (IAPP), are observed near pancreatic beta-cells of type II diabetics, with their presence strongly correlating with a loss of beta-cell mass and decreased pancreatic function. Although beta-cell membranes have been implicated as the likely target of amyloidogenic IAPP toxicity, interactions between membranes and IAPP in the fibrillar state have not been well characterized. In this study, turbidity measurements were conducted to provide a detailed description of the binding reaction between IAPP fibrils and lipid vesicles made from phosphatidylcholine. The kinetic data representing the rate and extent of the fibril-vesicle binding reaction are described well by an empirical double-exponential equation. The extent of binding was found to increase with increasing amyloid fibril concentration. Modification of the vesicle composition significantly altered the observed binding reaction kinetics, with the change quantified using the parameters obtained from the double-exponential fitting analysis. When the vesicles contained a significant amount of the lipid phosphatidylglycerol, substantial sedimentation of the vesicles under gravity was detected following the initial binding reaction. To rationalize the observed kinetic binding data, we developed a mesoscopic simulation model based on a hard particle representation of the species involved. In light of the observed data and simulation predictions, the potential roles of IAPP amyloid fibrils in membrane binding are discussed.
authors.affiliation: Division of Structural Biology, Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. sasahara@med.kobe-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Sasahara
authors.forename: Damien
authors.initials: D
authors.lastname: Hall
authors.forename: Daizo
authors.initials: D
authors.lastname: Hamada
mesh_terms: D000465:Algorithms; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D008567:Membranes, Artificial; D009391:Nephelometry and Turbidimetry; D010713:Phosphatidylcholines / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D011485:Protein Binding; D013109:Sphingomyelins / Q000737:chemistry
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D058228:Islet Amyloid Polypeptide; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines; D013109:Sphingomyelins