Membrane fragmentation by an amyloidogenic fragment of human Islet Amyloid Polypeptide detected by solid-state NMR spectroscopy of membrane nanotubes |
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Authors: | Jeffrey R. Brender Deborah Heyl Ayyalusamy Ramamoorthy |
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Affiliation: | a Biophysics and Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA b Department of Chemistry, Eastern Michigan University, Ypsilanti, MI 48197, USA |
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Abstract: | A key factor in the development of Type II diabetes is the loss of insulin producing pancreatic β-cells. The amyloidogenic human Islet Amyloid Polypeptide (hIAPP also known as human amylin) is believed to play a crucial role in this biological process. Previous studies have shown that hIAPP forms small aggregates that kill β-cells by disrupting the cellular membrane. In this study, we report membrane fragmentation by hIAPP using solid-state NMR experiments on nanotube arrays of anodic aluminum oxide containing aligned phospholipid membranes. In a narrow concentration range of hIAPP, an isotropic 31P chemical shift signal indicative of the peptide-induced membrane fragmentation was detected. Solid-state NMR results suggest that membrane fragmentation is related to peptide aggregation as the presence of Congo Red, an inhibitor of amyloid formation, prevented membrane fragmentation and the non-amyloidogenic rat-IAPP did not cause membrane fragmentation. The disappearance of membrane fragmentation at higher concentrations of hIAPP suggests an alternate kinetic pathway to fibril formation in which membrane fragmentation is inhibited. |
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Keywords: | Islet Amyloid Polypeptide Amylin Solid-Stat NMR Membrane Nanotubes |
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