Aggregation of amyloid beta protein under different shearing conditions: Experiments and modelling

Amyloid proteins are prone to form insoluble fibrillar aggregates, which have implications in various neurodegenerative diseases. While the monomers themselves are not toxic, their assembly into oligomers and fibrillar forms are harmful. There is a multi-fold increase in the fibrillation rate when the peptide solution is stirred, shaken, or agitated. In this work, steady and unsteady shear experiments are performed on Aβ40 solution using a Couette cell and orbital shaker, respectively. Under steady shear, there is an increase in both the mass of fibrils and aggregation rate with the shear rate. When shaken, the lag time decreases with an increase in the rotational speed of the shaker. A population balance model is developed to account for the effect of steady and unsteady shear on the aggregation of Aβ40 to explain these contrasting mechanisms of aggregation kinetics. The kinetic model includes the primary nucleation, elongation, fragmentation, and depolymerization steps. The effect of steady shear is captured by the depolymerization rate constant (kd). It is observed that the kd decreases with shear rate initially and saturates at high shear rates. The population balance model results agree quantitatively well with the experimental data.