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Int. J. Mol. Sci. 2018, 19(5), 1357; https://doi.org/10.3390/ijms19051357

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

1
Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK
2
Department of Bioengineering, Imperial College London, London SW7 2AZ, UK
3
Department of Physics, University of Liverpool, Liverpool L69 7ZE, UK
*
Author to whom correspondence should be addressed.
Received: 7 March 2018 / Revised: 25 April 2018 / Accepted: 1 May 2018 / Published: 3 May 2018
(This article belongs to the Special Issue Atomic Force Microscopy for Biological Applications)
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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. View Full-Text
Keywords: atomic force microscopy; amyloid; aortic medial amyloid/medin; mathematical modelling; aggregation atomic force microscopy; amyloid; aortic medial amyloid/medin; mathematical modelling; aggregation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Davies, H.A.; Lee, C.F.; Miller, L.; Liu, L.-N.; Madine, J. Insights into the Origin of Distinct Medin Fibril Morphologies Induced by Incubation Conditions and Seeding. Int. J. Mol. Sci. 2018, 19, 1357.

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