Gel vs. Plaque Formation during Self-assembly of Amyloid Fibrils

Self-assembly of proteins into amyloid fibrils plays a key role in both functional biological responses and pathogenic disorders, which include Alzheimer’s disease and type II diabetes. Much effort has focused on the formation of individual fibrils and oligomeric intermediates formed during fibril growth. However, for understanding the pathological effects of amyloid fibrils as well as for their application in functional biomaterials, it is equally important to understand the types of fibrillar suprastructures they tend to form. Using pre-formed amyloid fibrils, we investigated their self-assembly into larger supramolecular fibril networks as function of charge screening and solution pH. At acidic pH, increasing charge screening caused lysozyme amyloid to assemble into disordered gel clusters. In contrast, fibril self-assembly at neutral pH induced rapid formation of compact, nearly two-dimensional fibril sheets. The latter displayed localized birefringence considered hallmarks of amyloid plaques in vivo. Our observations suggest that the pH-dependent charge distribution of the monomers within the fibrils plays a significant role in fibril self-assembly. This provides an adjustable parameter for modulating the self-assembly behavior of amyloid fibrils into larger suprstructures.







This work was supported in part by National Science Foundation under award DMR-1852269.