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SUMMARY:Nucleation and growth of insulin fibrils in bulk solution and at h
 ydrophobic polystyrene surfaces - Dr. James Sharp\, School of Physics and 
 Astronomy and Nottingham Nanotechnology and Nanoscience Centre\, Universit
 y of Nottingham
DTSTART:20090522T131500Z
DTEND:20090522T141500Z
UID:TALK16799@talks.cam.ac.uk
CONTACT:Jurij Kotar
DESCRIPTION:The abundance of interfaces in vivo has resulted in a signific
 ant amount of interest in trying to understand the influence of surfaces a
 nd interfaces on protein aggregation. The large surface to volume ratios o
 f high surface area and nanoscale materials being developed for the new ge
 neration of nanomedicines and diagnostic applications are a potential conc
 ern and highlight the importance of understanding the impact of interfaces
  on protein aggregation processes.\n\nIn this study\, fourier transform in
 fra-red spectroscopy was used to monitor the changes in inter-molecular β
 -sheet content of bovine pancreatic insulin at pH 1 and over a range of te
 mperatures (60°C - 80°C) in bulk solution and at a polystyrene surface (
 PS). The formation of inter-molecular β-sheet was found to be a two stage
  process. The first stage in β-sheet growth corresponded to the formation
  of prefibrillar aggregates (~13nm) and the second stage was attributed to
  the formation of fibrils. The -sheet formation kinetics were used to s
 how that prefibrillar aggregates play an important role in the nucleation 
 of insulin fibrils. They were also used to determine the nucleation and gr
 owth rates associated with fibril formation for both the PS surfaces and b
 ulk solution data. The resulting Arrhenius kinetics enabled the determinat
 ion of the associated activation energies.\n\nThese experiments show that 
 the PS surfaces nucleate fibrils more quickly\, but that fibril growth is 
 slower than in bulk solution.  These results are interpreted in terms of t
 he differences in concentration\, mobility\, conformational and colloidal 
 stability of the protein molecules adsorbed at surfaces when compared to s
 imilar molecules in bulk solution.\n
LOCATION:Small Lecture Theatre\, Cavendish Laboratory
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