title: Influence of the Human and Rat Islet Amyloid Polypeptides on Structure of Phospholipid Bilayers: Neutron Reflectometry and Fluorescence Microscopy Studies.
abstract: Neutron reflectivity (NR) and fluorescent microscopy (FM) were used to study the interactions of human (hIAPP) and rat (rIAPP) islet amyloid polypeptides with several formulations of supported model lipid bilayers at the solid-liquid interface. Aggregation and deposition of islet amyloid polypeptide is correlated with the pathology of many diseases, including Alzheimer's, Parkinson, and type II diabetes (T2DM). A central component of T2DM pathology is the deposition of fibrils in the endocrine pancreas, which is toxic to the insulin secreting β-cells. The molecular mechanism by which the cell death occurs is not yet understood, but existing evidence points toward interactions of IAPP oligomers with cellular membranes in a manner leading to loss of their integrity. Our NR and FM results showed that the human sequence variant, hIAPP, had little or no effect on bilayers composed of saturated-acyl chains like zwitterionic DPPC, anionic DPPG, and mixed 80:20 mol % DPPC:DPPG bilayers. In marked contrast, the bilayer structure and stability of anionic unsaturated DOPG were sensitive to protein interaction, and the bilayer was partly solubilized by hIAPP under the conditions used here. The rIAPP, which is considered less toxic, had no perturbing effects on any of the above membrane formulations. Understanding the conditions that result in membrane disruption by hIAPP can be crucial in developing counter strategies to fight T2DM and also physicochemically similar neurodegenerative diseases such as Alzheimer's.
authors.forename: Ann
authors.initials: A
authors.lastname: Junghans
authors.forename: Erik B
authors.initials: EB
authors.lastname: Watkins
authors.affiliation: Department of Chemical Engineering University of California, Davis , Davis, California 95616, United States.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Majewski
authors.affiliation: Department of Molecular Biophysics & Biochemistry, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Miranker
authors.affiliation: Worcester Polytechnic Institute, Worcester, Massachusetts 01609, United States.
authors.forename: Izabela
authors.initials: I
authors.lastname: Stroe
mesh_terms: D000818:Animals; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry / Q000494:pharmacology*; D008051:Lipid Bilayers / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D033363:Neutron Diffraction; D011487:Protein Conformation; D051381:Rats
chemical_list: D058228:Islet Amyloid Polypeptide; D008051:Lipid Bilayers