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

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...

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Detalles Bibliográficos
Autores principales: Davies, Hannah A., Lee, Chiu Fan, Miller, Leanne, Liu, Lu-Ning, Madine, Jillian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983645/
https://www.ncbi.nlm.nih.gov/pubmed/29751581
http://dx.doi.org/10.3390/ijms19051357
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author Davies, Hannah A.
Lee, Chiu Fan
Miller, Leanne
Liu, Lu-Ning
Madine, Jillian
author_facet Davies, Hannah A.
Lee, Chiu Fan
Miller, Leanne
Liu, Lu-Ning
Madine, Jillian
author_sort Davies, Hannah A.
collection PubMed
description 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.
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spelling pubmed-59836452018-06-05 Insights into the Origin of Distinct Medin Fibril Morphologies Induced by Incubation Conditions and Seeding Davies, Hannah A. Lee, Chiu Fan Miller, Leanne Liu, Lu-Ning Madine, Jillian Int J Mol Sci Article 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. MDPI 2018-05-03 /pmc/articles/PMC5983645/ /pubmed/29751581 http://dx.doi.org/10.3390/ijms19051357 Text en © 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/).
spellingShingle Article
Davies, Hannah A.
Lee, Chiu Fan
Miller, Leanne
Liu, Lu-Ning
Madine, Jillian
Insights into the Origin of Distinct Medin Fibril Morphologies Induced by Incubation Conditions and Seeding
title Insights into the Origin of Distinct Medin Fibril Morphologies Induced by Incubation Conditions and Seeding
title_full Insights into the Origin of Distinct Medin Fibril Morphologies Induced by Incubation Conditions and Seeding
title_fullStr Insights into the Origin of Distinct Medin Fibril Morphologies Induced by Incubation Conditions and Seeding
title_full_unstemmed Insights into the Origin of Distinct Medin Fibril Morphologies Induced by Incubation Conditions and Seeding
title_short Insights into the Origin of Distinct Medin Fibril Morphologies Induced by Incubation Conditions and Seeding
title_sort insights into the origin of distinct medin fibril morphologies induced by incubation conditions and seeding
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983645/
https://www.ncbi.nlm.nih.gov/pubmed/29751581
http://dx.doi.org/10.3390/ijms19051357
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