The mechanism of amyloid spherulite formation by bovine insulin.
The formation of amyloid-containing spherulite-like structures has been observed in some instances of amyloid diseases, as well as in amyloid fibril-containing solutions in vitro. In this article we describe the structure and kinetics of bovine insulin amyloid fibril spherulites formed in the presence and absence of different salts and at different salt concentrations. The general spherulite structure consists of radially oriented amyloid fibrils, as shown by optical microscopy and environmental scanning electron microscopy. In the center of each spherulite, a "core" of less regularly oriented material is observed, whose size decreases when the spherulites are formed in the presence of increasing concentrations of NaCl. Similarly, amyloid fibrils form faster in the presence of NaCl than in its absence. A smaller enhancement of the rate of formation with salt concentration is observed for spherulites. These data suggest that both amyloid fibril formation and random aggregation occur concurrently under the conditions tested. Changes in their relative rates result in the different-sized cores observed in the spherulites. This mechanism can be likened to that leading to the formation of spherulites of polyethylene, in agreement with observations that polypeptide chains under partially denaturing conditions can exhibit behavior not dissimilar to that of synthetic polymers.
Krebs
M R H
MR
Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, Madingley Rd., Cambridge CB3 0HE, UK. mrhk2@cam.ac.uk
Bromley
E H C
EH
Rogers
S S
SS
Donald
A M
AM
D000682:Amyloid / Q000032:analysis / Q000737:chemistry* / Q000648:ultrastructure*; D000818:Animals; D002417:Cattle; D003460:Crystallization / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000032:analysis / Q000737:chemistry*; D007700:Kinetics; D046912:Multiprotein Complexes / Q000032:analysis / Q000737:chemistry; D011487:Protein Conformation; D011489:Protein Denaturation; D012965:Sodium Chloride / Q000737:chemistry*
D000682:Amyloid; D007328:Insulin; D046912:Multiprotein Complexes; D012965:Sodium Chloride