Detailed Mechanism of Rapid Amyloid Fibril Self-Assembly Due to Surface Diffusion

Abstract

Surface-mediated fibrillization has been considered as an alternative pathway to form amyloid fibrils under physiological conditions. In order to develop new probes and therapies for neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, it's important to explore the detailed mechanism of the surface effects. However, the surface morphologies change with time and are hard to image without staining or labeling, which may alter the process of self-assembly. In recent work, we demonstrated a label-free procedure via controlling incubation time and the drying process to monitor the kinetics of fibril growth on surfaces across many length scales. We propose an anisotropic growth model to fit the time-evolution of morphologies of amyloid fibrils forming near a surface as measured using Atomic force microscopy (AFM). Two important variables, the deposition rate and the two-dimensional diffusion coefficient, can be used as fitting variables and can be characterized by the combination of experimental data and the theoretical approach presented here.