Probing physical properties of single amyloid fibrils using nanofluidic channels

Other conference contribution, 2023

Amyloid fibrils formation via protein misfolding and aggregation is associated with many diseases, including neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. The presence of polymorphism phenomenon in a single protein sample makes it important to analyze amyloid fibrils on the single fibril level. We here introduce the concept of nanofluidic channel analysis to the study of single, fluorescently labeled amyloid fibrils. The confinement of amyloid fibrils in nanochannels makes it possible to measure their extension at each width as well as their emission intensity. We used Odijk’s theory for strongly confined polymers to determine the persistence length of each fibril. A majority of the persistence lengths were in the 1-10 m regime and for both the Alzheimer’s protein amyloid- (1-42) and the Parkinson’s protein-synuclein we find at least two populations of fibrils with different persistence lengths, indicating the coexistence of polymorphs with different physical properties. We foresee that the nanofluidics methodology that we have established here will be a useful future tool to study amyloid fibrils on the single fibril level to inform on heterogeneity in their physical properties and interactions.