Nano-Scaled Three-Dimensional Fibrillar Network Made of Curly Amyloid Fibrils of α-Synuclein

Abstract

Amyloid fibrils are highly organized protein suprastructures derived from soluble peptides and proteins through the specific self-assembly process. From a single amyloidogenic protein of α-synuclein, two distinctive amyloid fibrils were produced depending on the fibrillation processes. The polymorphism resulting in formation of curly (CAF) and straight amyloid fibrils (SAF) was respectively achieved with the centrifugal membrane filtration of the preformed α-synuclein oligomers and the agitated incubation of its monomeric form. It is demonstrated that the production of CAF and SAF represents two parallel mechanisms of amyloidogenesis via double-concerted and nucleation-dependent fibrillation process, respectively. Differences in their secondary structures of the polymorphs have been suggested to be responsible for their characteristic morphologies with significant variations in physical properties, which were inherited for two consecutive generations to the daughter and granddaughter fibrils by self-propagation property. Accumulation of highly flexible and mechanically strong CAF eventually produced the hydrogel composed of the three-dimensional fibrillar network in fine nano-scale. The amyloid hydrogel was proven to be a suitable nanomatrix for enzyme entrapment, protecting the immobilized enzyme from the activity decrease due to repetitive catalytic reactions and heat treatment. Therefore, the nano-scaled fibrillar network of CAF is expected to be employed for various future applications in nanobiotechnology including drug delivery, tissue engineering and biosensor development.