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

International Journal of Molecular Sciences
Hannah A DaviesJillian Madine

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.

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Citations

Oct 21, 2020·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Monika KrupováPetr Bouř
May 14, 2020·Biophysical Journal·Scott YoungerFernando T Arce
Feb 24, 2020·International Journal of Biological Macromolecules·Masoud DelfiDelia Picone

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Methods Mentioned

BETA
circular
nuclear
atomic force microscopy
NMR
AFM
Fluorescence
circular dichroism

Software Mentioned

Topsin
Olis GlobalWorks
Gwyddion
Topspin
CONTINLL
CCPN Analysis
NanoScope

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