Shear flow promotes amyloid-β fibrilization.

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Bibliographic Details
Title:	Shear flow promotes amyloid-β fibrilization.
Authors:	Dunstan, Dave E.¹ davided@unimelb.edu.au, Hamilton-Brown, Paul¹, Asimakis, Peter¹, Ducker, William¹, Bertolini, Joseph²
Source:	PEDS: Protein Engineering, Design & Selection. Dec2009, Vol. 22 Issue 12, p741-746. 6p. 2 Black and White Photographs, 3 Graphs.
Subjects:	Amyloid beta-protein, Atomic force microscopy, Molecules, Proteins, Alzheimer's disease
Abstract:	The rate of formation of amyloid fibrils in an aqueous solution of amyloid-β (Aβ) is greatly increased when the solution is sheared. When Aβ solution is stirred with a magnetic stirrer bar at 37°C, a rapid increase in thioflavin T fluorescence is observed. Atomic Force Microscopy (AFM) images show the formation of aggregates, the growth of fibrils and the intertwining of the fibrils with time. Circular dichroism (CD) spectroscopy of samples taken after stirring shows a transition from random coil to α-helix to β-sheet secondary structure over 20 h at 37°C. The fluorescence, AFM and CD measurements are all consistent with the formation of amyloid fibrils. Quiescent, non-stirred solutions incubated at 37°C showed no evidence of amyloid formation over a period of 3 days. Couette flow was found to accelerate the formation of amyloid fibrils demonstrating that the primary effect of stirring is not mixing but shearing. Only very small shear forces are applied to individual molecules in our experiments. Simple calculation suggests that the force is too small to support a hypothesis that shearing promotes partial unfolding of the protein as is observed. [ABSTRACT FROM PUBLISHER]
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Database:	Engineering Source

Description
Abstract:	The rate of formation of amyloid fibrils in an aqueous solution of amyloid-β (Aβ) is greatly increased when the solution is sheared. When Aβ solution is stirred with a magnetic stirrer bar at 37°C, a rapid increase in thioflavin T fluorescence is observed. Atomic Force Microscopy (AFM) images show the formation of aggregates, the growth of fibrils and the intertwining of the fibrils with time. Circular dichroism (CD) spectroscopy of samples taken after stirring shows a transition from random coil to α-helix to β-sheet secondary structure over 20 h at 37°C. The fluorescence, AFM and CD measurements are all consistent with the formation of amyloid fibrils. Quiescent, non-stirred solutions incubated at 37°C showed no evidence of amyloid formation over a period of 3 days. Couette flow was found to accelerate the formation of amyloid fibrils demonstrating that the primary effect of stirring is not mixing but shearing. Only very small shear forces are applied to individual molecules in our experiments. Simple calculation suggests that the force is too small to support a hypothesis that shearing promotes partial unfolding of the protein as is observed. [ABSTRACT FROM PUBLISHER]
ISSN:	17410126
DOI:	10.1093/protein/gzp059