Influence of hydrophobicity on the surface-catalyzed assembly of the islet amyloid polypeptide.

The islet amyloid polypeptide (IAPP) is a hormonal factor secreted by the β-cells in the pancreas. Aggregation of misfolded IAPP molecules and subsequent assembly of amyloid nanofibrils are critical for the development of type 2 diabetes mellitus. In the physiological environment, amyloid aggregation is affected by the presence of interfaces such as cell membranes. The physicochemical properties of the interface dictates the interaction of the peptide with the surface, i.e., electrostatic and hydrophobic interactions on hydrophilic and hydrophobic surfaces, respectively. We have studied the influence of hydrophobicity on the surface-catalyzed assembly of IAPP on ultrasmooth hydrocarbon films grown on ion-beam-modified mica surfaces by atomic force microscopy. The contact angle θ of these surfaces can be tuned continuously in the range from ≤20° to ∼90° by aging the samples without significant changes of the chemical composition or the topography of the surface. On hydrophilic surfaces with a θ of ∼20°, electrostatic interactions induce the assembly of IAPP nanofibrils, whereas aggregation of large (∼2.6 nm) oligomers is observed at hydrophobic surfaces with a θ of ∼90°. At intermediate contact angles, the interplay between electrostatic and hydrophobic substrate interactions dictates the pathway of aggregation with fibrillation getting continuously delayed when the contact angle is increased. In addition, the morphology of the formed protofibrils and mature fibrils at intermediate contact angles differs from those observed at more hydrophilic surfaces. These results might contribute to the understanding of the surface-catalyzed assembly of different amyloid aggregates and may also have implications for the technologically relevant controlled synthesis of amyloid nanofibrils of desired morphology.