Insulin fibril nucleation: the role of prefibrillar aggregates
Michael I Smith 1, James S Sharp 1* and Clive J Roberts 1
1 University of Nottingham
* To whom correspondence should be addressed. E-mail: james.sharp{at}nottingham.ac.uk.
Submitted on February 15, 2008
Revised on April 10, 2008
Accepted on 10 June 2008
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Abstract |
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Dynamic light scattering and Fourier Transform Infrared (FTIR) spectroscopy were used to study the formation of prefibrillar aggregates and fibrils of bovine pancreatic insulin (BPI) at 60$ °C and at pH1. The kinetics of disintegration of the prefibrillar aggregates were also studied using these techniques following a quench to 25°C. These experiments reveal that formation of prefibrillar aggregates is reversible under the solution conditions studied and show that it is possible to significantly reduce the nucleation (lag) times associated with the onset of fibril growth in BPI solutions by increasing the concentration of prefibrillar aggregates in solution. These results provide convincing evidence that less structured prefibrillar aggregates can act as fibril forming intermediates.
Key Words:
Amyloid fibrils, Insulin, dynamic light scattering, ftir spectrosopy, nucleation, protein
