2D amyloid aggregation of human islet amyloid polypeptide at the solid–liquid interface

Abstract

Protein misfolding, aggregation, and amyloid deposits are the common hallmarks of amyloid diseases, such as Alzheimer's disease, type 2 diabetes mellitus (T2DM), Huntington disease, prion disease, and Parkinson's disease. In the case of T2DM, the aggregation of human islet amyloid polypeptide (hIAPP) accumulates in the pancreatic islets, which has the ability to grow into different aggregation states. Increasing evidence strongly suggests that the hIAPP aggregation process itself rather than the amyloid fibrils is the crucial trigger of β-cell apoptosis. Recent studies indicate that hIAPP aggregation was enhanced strongly by negatively charged membranes. Potentially toxic prefibrillar species are generated when hIAPP interacts with membranes, which indicates the relationship between protein–membrane interaction and hIAPP-induced β cell dysfunction. Therefore the hIAPP aggregation pathway can be greatly influenced by the presence of surface. Here we investigate how biocompatible surfaces, like negative charged tantalum oxide, influence hIAPP aggregation. We investigate the formation of hIAPP in the bulk solution using fluorescence assay and atomic force microscopy (AFM) techniques under physiological buffer conditions to identify the detailed nanoscale structures of hIAPP assembly. High resolution AFM images show hIAPP assembled into nanofibrils with characteristics of knot structures after incubation in the bulk solution. By using a quartz crystal microbalance with dissipation combined with liquid AFM, the dynamic kinetic processes of hIAPP assembly on the solid–liquid interface can be monitored, and it shows that the tantalum oxide surface induces 2D homogeneous protofibrils formation without knot structures. These observations point toward a novel surface-involved pathway of protein adsorption and 2D amyloid aggregation, which allows us to reveal the in vivo mechanism of surface-involved amyloid accumulation in the pathology of T2DM.