Heparin assisted assembly of somatostatin amyloid nanofibrils results in disordered precipitates by hindrance of protofilaments interactions

Nanoscale
Durga DharmadanaCéline Valéry

Abstract

Amyloid nanofibrils are β-sheet rich protein or peptide assemblies that have pathological roles in over 20 neurodegenerative diseases, but also can have essential physiological roles. This wide variety of functions is likely to be due to subtle differences in amyloid structure and assembly mechanisms. Glycosaminoglycans (GAGs), like heparin, are frequently used in vitro to increase the kinetics of assembly of amyloid fibrils. However, little is known about the effects of adding large polymeric sugars on assembly mechanisms and amyloid nanostructures. Here, we provide insights into the kinetics, assembly mechanisms and structural effects of heparin on the self-assembly of a functional-amyloid forming neuropeptide hormone, somatostatin-14. We show that pure somatostatin-14 self-assembles into amyloid fibrils via the formation of antiparallel β-sheet networks, in a typical amyloid aggregation process. These fibrils then laterally assemble into ordered liquid crystalline structures through the generation of further parallel β-sheet networks. If heparin molecules are present, they intercalate between the peptide assemblies during the initial stages of aggregation. This intercalation screens electrostatic repulsions hindering the lat...Continue Reading

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Citations

Feb 27, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mariana I NevesCristina C Barrias
Jan 10, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Enric Mayans, Carlos Alemán
May 31, 2019·Biomacromolecules·Hugh D GlossopVijayalekshmi Sarojini
Sep 21, 2021·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Benjamin J Van TreeckSamar Said

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Methods Mentioned

BETA
biosensing
NMR
X-ray
atomic force microscopy
electron microscopy
AFM
infrared spectroscopy
transmission electron microscopy

Software Mentioned

ATSAS
opus
Gatan
Nanoscope Analysis
Prism GraphPad
QNM
Primus
Guinier
FiberApp

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