title: Comparison of Human and Bovine Insulin Amyloidogenesis under Uniform Shear.
abstract: A diverse range of proteins can assemble into amyloid fibrils, a process that generally results in a loss of function and an increase in toxicity. The occurrence and rate of conversion is strongly dependent on several factors including molecular structure and exposure to hydrodynamic forces. To investigate the origins of shear-induced enhancement in the rate of fibrillization, a stable rotating Couette flow was used to evaluate the kinetics of amyloid formation under uniform shear for two similar insulin species (human and bovine) that demonstrate unique fibrillization kinetics. The presence of shear-induced nuclei predicted by previous studies is supported by observations of a lag between the consumption of soluble insulin and the precipitation of amyloid aggregates. The apparent fibrillization rate generally increases with shear. However, a two-parameter kinetic model revealed that the nucleation rate has a maximum value at intermediate shear rates. The fibril elongation rate increases monotonically with shear and is similar for both insulin variants, suggesting that increased elongation rates are related to mixing. Differences between human and bovine insulin kinetics under shear are attributable to the nucleation step.
authors.affiliation: †Department of Chemical and Biological Engineering, ‡Department of Mechanical, Aerospace, and Nuclear Engineering, and §Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York 12180, United States.
authors.forename: Samantha A
authors.initials: SA
authors.lastname: McBride
authors.affiliation: †Department of Chemical and Biological Engineering, ‡Department of Mechanical, Aerospace, and Nuclear Engineering, and §Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York 12180, United States.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Tilger
authors.affiliation: †Department of Chemical and Biological Engineering, ‡Department of Mechanical, Aerospace, and Nuclear Engineering, and §Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York 12180, United States.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Sanford
authors.affiliation: †Department of Chemical and Biological Engineering, ‡Department of Mechanical, Aerospace, and Nuclear Engineering, and §Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York 12180, United States.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Tessier
authors.affiliation: †Department of Chemical and Biological Engineering, ‡Department of Mechanical, Aerospace, and Nuclear Engineering, and §Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York 12180, United States.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Hirsa
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D006801:Humans; D057446:Hydrodynamics; D007328:Insulin / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D033081:Shear Strength
chemical_list: D000682:Amyloid; D007328:Insulin