Maturation-dependent changes in the size, structure and seeding capacity of Aβ42 amyloid fibrils

• Published in: Communications biology Vol. 7; no. 1; p. 153
• Main Authors: Miller, Alyssa, Chia, Sean, Klimont, Ewa, Knowles, Tuomas P. J., Vendruscolo, Michele, Ruggeri, Francesco Simone
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.02.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 101/62; 14/3; 631/535/1262; 631/57/2265; Aggregates; Amyloid; Atomic force microscopy; Biology; Biomaterials; Biomedical and Life Sciences; Biomedical materials; Catalysis; Chemistry; Disease; Fibrillogenesis; Fourier transforms; Hydrogen bonding; Intermediates; Investigations; Kinetics; Life Sciences; Maturation; Microscopy; NMR; Nuclear magnetic resonance; Protein seeding; Proteins; Seeds
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-05858-7

Many proteins self-assemble to form amyloid fibrils, which are highly organized structures stabilized by a characteristic cross-β network of hydrogen bonds. This process underlies a variety of human diseases and can be exploited to develop versatile functional biomaterials. Thus, protein self-assembly has been widely studied to shed light on the properties of fibrils and their intermediates. A still open question in the field concerns the microscopic processes that underlie the long-time behaviour and properties of amyloid fibrillar assemblies. Here, we use atomic force microscopy with angstrom-sensitivity to observe that amyloid fibrils undergo a maturation process, associated with an increase in both fibril length and thickness, leading to a decrease of their density, and to a change in their cross-β sheet content. These changes affect the ability of the fibrils to catalyse the formation of new aggregates. The identification of these changes helps us understand the fibril maturation processes, facilitate the targeting of amyloid fibrils in drug discovery, and offer insight into the development of biocompatible and sustainable protein-based materials. Microspray, nano-imaging and chemical analysis reveal time-dependent changes in the structural properties of amyloid fibrils in their plateau phase, conferring changes on the fibril surfaces for secondary nucleation and catalysis of aggregation.