title: Chiral superstructures of insulin amyloid fibrils.
abstract: Hydrodynamic forces are capable of inducing structural order in dispersed solid phases, and of causing symmetry-breaking when chiral crystals precipitate from an achiral liquid phase. Until it was observed upon vortex-assisted fibrillation of insulin, such behavior had been thought to be confined to few unbiological systems. In this paper we are discussing chiroptical properties of two chiral variants of insulin amyloid, termed +ICD and -ICD, which form during the process of chiral bifurcation in vortexed solutions of aggregating insulin. As conventional measurements of circular dichroism of solid, anisotropic substances are particularly vulnerable to overlapping influences of linear birefringence and linear dichroism, we have employed complementary tools including dedicated universal chiroptical spectrophotometer to rule out such artifacts. We propose that the strong chiroptical properties of +ICD and -ICD insulin fibrils are an aspect of genuine superstructural chirality of amyloid fibrils and of powerful excitonic couplings taking place within them. A comparison of thioflavin T complexes with fibrils formed by insulin and polyglutamic acid suggests that the extrinsic Cotton effect stemming from the level of single twisted dye molecules is weaker, although diagnostically useful, and cannot account for the overall magnitude of ICD of the dye bound to ±ICD insulin amyloid.
authors.affiliation: Department of Chemistry, University of Warsaw, Warsaw, Poland.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Babenko
authors.forename: Takunori
authors.initials: T
authors.lastname: Harada
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yagi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
authors.forename: Reiko
authors.initials: R
authors.lastname: Kuroda
authors.forename: Wojciech
authors.initials: W
authors.lastname: Dzwolak
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D052160:Benzothiazoles; D001718:Birefringence; D002942:Circular Dichroism / Q000379:methods*; D007328:Insulin / Q000737:chemistry*; D017510:Protein Folding; D055503:Protein Multimerization; D013844:Thiazoles / Q000737:chemistry
chemical_list: D000682:Amyloid; D052160:Benzothiazoles; D007328:Insulin; D013844:Thiazoles; C009462:thioflavin T