Membrane fragmentation by an amyloidogenic fragment of human Islet Amyloid Polypeptide detected by solid-state NMR spectroscopy of membrane nanotubes.
A key factor in the development of Type II diabetes is the loss of insulin producing pancreatic beta-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 beta-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 (31)P 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.
Brender
Jeffrey R
JR
Biophysics and Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA.
Dürr
Ulrich H N
UH
Heyl
Deborah
D
Budarapu
Mahender B
MB
Ramamoorthy
Ayyalusamy
A
D000537:Aluminum Oxide / Q000737:chemistry; D000682:Amyloid; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D006801:Humans; D007515:Islets of Langerhans / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000737:chemistry*; D008567:Membranes, Artificial; D008968:Molecular Conformation; D043942:Nanotubes / Q000737:chemistry*; D010446:Peptide Fragments; D010539:Permeability; D016062:Porosity
D000682:Amyloid; D008563:Membrane Lipids; D008567:Membranes, Artificial; D010446:Peptide Fragments; D000537:Aluminum Oxide; D004134:Dimyristoylphosphatidylcholine