NDLI: Perturbation of the Stability of Amyloid Fibrils through Alteration of Electrostatic Interactions

Content Provider	PubMed Central
Author	Shammas, Sarah L. Knowles, Tuomas P. J. Baldwin, Andrew J. Macphee, Cait E. Welland, Mark E. Dobson, Christopher M. Devlin, Glyn L.
Copyright Year	2011
Abstract	The self-assembly of proteins and peptides into polymeric amyloid fibrils is a process that has important implications ranging from the understanding of protein misfolding disorders to the discovery of novel nanobiomaterials. In this study, we probe the stability of fibrils prepared at pH 2.0 and composed of the protein insulin by manipulating electrostatic interactions within the fibril architecture. We demonstrate that strong electrostatic repulsion is sufficient to disrupt the hydrogen-bonded, cross-β network that links insulin molecules and ultimately results in fibril dissociation. The extent of this dissociation correlates well with predictions for colloidal models considering the net global charge of the polypeptide chain, although the kinetics of the process is regulated by the charge state of a single amino acid. We found the fibrils to be maximally stable under their formation conditions. Partial disruption of the cross-β network under conditions where the fibrils remain intact leads to a reduction in their stability. Together, these results support the contention that a major determinant of amyloid stability stems from the interactions in the structured core, and show how the control of electrostatic interactions can be used to characterize the factors that modulate fibril stability.
Related Links	http://dx.doi.org/10.1016/j.bpj.2011.04.039
Ending Page	2791
Page Count	9
Starting Page	2783
File Format	PDF
ISSN	00063495
e-ISSN	15420086
Journal	Biophysical Journal
Issue Number	11
Volume Number	100
Language	English
Publisher	The Biophysical Society
Publisher Date	2011-06-01
Access Restriction	Open
Rights Holder	The Biophysical Society
Subject Keyword	Biophysics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Biophysics

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