Insights into the origin of distinct medin fibril morphologies induced by incubation conditions and seeding.
File(s)
Accepted version
Author(s)
Lee, C
Leanne, M
Liu, L-N
Madine, J
Davies, H
Type
Journal Article
Abstract
Incubation conditions are an important factor to consider when studying protein aggregation in vitro. Here, we employed biophysical methods and atomic force microscopy to show that agitation dramatically alters the morphology of medin, an amyloid protein deposited in the aorta. Agitation reduces the lag time for fibrillation by ~18-fold, suggesting that the rate of fibril formation plays a key role in directing the protein packing arrangement within fibrils. Utilising preformed sonicated fibrils as seeds, we probed the role of seeding on medin fibrillation and revealed three distinct fibril morphologies, with biophysical modelling explaining the salient features of experimental observations. We showed that nucleation pathways to distinct fibril morphologies may be switched on and off depending on the properties of the seeding fibrils and growth conditions. These findings may impact on the development of amyloid-based biomaterials and enhance understanding of seeding as a pathological mechanism.
Date Issued
2018-05-03
Date Acceptance
2018-05-01
Citation
International Journal of Molecular Sciences, 2018, 19 (5)
ISSN
1661-6596
Publisher
MDPI AG
Journal / Book Title
International Journal of Molecular Sciences
Volume
19
Issue
5
Copyright Statement
© 2018 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
License URL
Subjects
aggregation
amyloid
aortic medial amyloid/medin
atomic force microscopy
mathematical modelling
0399 Other Chemical Sciences
0604 Genetics
0699 Other Biological Sciences
Chemical Physics
Publication Status
Published
Date Publish Online
2018-05-03