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Insights into the origin of distinct medin fibril morphologies induced by incubation conditions and seeding

DOI: 10.3390/ijms19051357 DOI Help

Authors: Hannah A. Davies (University of Liverpool) , Chiu Fan Lee (Imperial College London) , Leanne Miller (University of Liverpool) , Lu-Ning Liu (University of Liverpool) , Jillian Madine (University of Liverpool)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: International Journal Of Molecular Sciences , VOL 19

State: Published (Approved)
Published: May 2018
Diamond Proposal Number(s): 8979

Open Access Open Access

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.

Journal Keywords: atomic force microscopy; amyloid; aortic medial amyloid/medin; mathematical modelling; aggregation

Subject Areas: Biology and Bio-materials


Instruments: B23-Circular Dichroism

Added On: 21/05/2018 12:02

Discipline Tags:

Biophysics Life Sciences & Biotech

Technical Tags:

Spectroscopy Circular Dichroism (CD)