Vortex-induced chiral bifurcation in aggregating insulin

Chiral symmetry breaking occurs during vortex-assisted crystallization of several simple compounds leading to a stochastically determined emergence of an enantiomeric excess of one chiral isomer. This article summarizes recent developments in studies of a similar phenomenon observed in agitated solutions of aggregating insulin, when a phase transition-precipitation of insoluble amyloid fibrils from solutions of the native protein-is coupled to a conformational transition of the native alpha-helical structure into aggregated beta-sheets. In contrast to the previously known cases of chiral bifurcation, the substrate is built of L-amino acids and, therefore, chirally biased. However, under certain conditions, insulin forms fibrils with superstructural chiral features that are independent of the left-handedness of amino acid residues, as revealed by the sign of extrinsic Cotton effect induced in amyloid-bound achiral dye-thioflavin T. The inherent chiral bias of the protein results in a diastereomeric relationship between the two optical isomers of amyloid superstructures and the fact that relative probability of formation of either isomer is temperature dependent. As the formation of amyloid fibrils in vivo is associated with several degenerative disorders such as Alzheimer's disease, this newly observed phenomenon may have important implications in the context of structural basis of biological activity of misfolded proteins.