Conformational memory effect reverses chirality of vortex-induced insulin amyloid superstructures.

Formation of amyloid fibrils is often associated with intriguing far-from-equilibrium phenomena such as conformational memory effects or flow-driven self-assembly. Insulin is a model amyloidogenic polypeptide forming distinct structural variants of fibrils, which self-propagate through seeding. According to infrared absorption, fibrils from bovine insulin ([BI]) and Lys(B31)-Arg(B32) human insulin analogue ([KR]) cross-seed each other and imprint distinct structural features in daughter fibrils. In the absence of preformed [KR] amyloid seeds, bovine insulin agitated at 60 °C converts into chiral amyloid superstructures exhibiting negative extrinsic Cotton effect in bound thioflavin T. However, when agitated bovine insulin is simultaneously cross-seeded with [KR] amyloid, daughter fibrils reveal a positive extrinsic Cotton effect. Our study indicates that dramatic changes in global properties of amyloid superstructures may emerge from subtle conformational-level variations in single fibrils (e.g., alignment and twist of β-strands) that are encoded by memory effects.