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

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Miller, Alyssa 
Chia, Sean 
Klimont, Ewa 
Vendruscolo, Michele  ORCID logo

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.


Acknowledgements: We gratefully acknowledge funding from the Finlay Scholarship, Centre for Misfolding Diseases, and the Frances and Augustus Newman Foundation.

Funder: We gratefully acknowledge funding from the Finlay Scholarship and the Frances and Augustus Newman Foundation.

Humans, Amyloid, Protein Conformation, beta-Strand, Microscopy, Atomic Force
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Commun Biol
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Springer Science and Business Media LLC