Insights into the Origin of Distinct Medin Fibril Morphologies Induced by Incubation Conditions and Seeding

Davies, Hannah, Lee, Chiu Fan, Miller, Leanne, Liu, L ORCID: 0000-0002-8884-4819 and Madine, J ORCID: 0000-0001-9963-5871 (2018) Insights into the Origin of Distinct Medin Fibril Morphologies Induced by Incubation Conditions and Seeding. International Journal of Molecular Sciences, 19 (5). pp. 1-15.

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Abstract

Incubation conditions are an important factor to consider when studying proteinaggregationin vitro. Here, we employed biophysical methods and atomic force microscopy toshow that agitation dramatically alters the morphology of medin, an amyloid protein depositedin the aorta. Agitation reduces the lag time for fibrillation by ~18-fold, suggesting that the rateof 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 fibrillationand revealed three distinct fibril morphologies, with biophysical modelling explaining the salientfeatures of experimental observations. We showed that nucleation pathways to distinct fibrilmorphologies may be switched on and off depending on the properties of the seeding fibrils andgrowth conditions. These findings may impact on the development of amyloid-based biomaterialsand enhance understanding of seeding as a pathological mechanism.

Item Type:	Article
Uncontrolled Keywords:	atomic force microscopy, amyloid, aortic medial amyloid/medin, mathematical modelling, aggregation
Depositing User:	Symplectic Admin
Date Deposited:	03 May 2018 15:08
Last Modified:	19 Jan 2023 06:34
DOI:	10.3390/ijms19051357
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3020892