Polymer Engineering and Colloid Science Lab, Department of Chemical Engineering, Indian Institute of Technology Madras, Chennai 600036, India.
Eberhard Karls Universität Tübingen, ZMBP, Auf der Morgenstelle 32, 72076 Tübingen, Germany.
Colloids Surf B Biointerfaces. 2022 Jan;209(Pt 1):112156. doi: 10.1016/j.colsurfb.2021.112156. Epub 2021 Oct 21.
Amyloid β (Aβ40) is a class of amyloidogenic proteins known to aggregate into a fibrillar network. The rate of aggregation and fibril yield is sensitive to external energy input, such as shear. In this work, simple shear and shaking experiments are performed on Aβ40 solution using a Couette cell and an orbital shaker, respectively. Experiments show that, under uniform shear, both the mass of fibrils and aggregation rate increase with the shear rate. In the case of orbital shaking, the lag time decreases with the rotational speed of the shaker, but the final fibril mass is the same for all agitation speeds. To explain this contrasting behavior of aggregation kinetics, a population balance model is developed to account for the effect of shear on the aggregation of Aβ. The kinetic model includes primary nucleation, secondary nucleation, elongation, fragmentation, and depolymerization steps. The effect of steady uniform shear is encoded in the depolymerization rate constant (k), and it is shown that k decreases with shear rate initially and saturates at high shear rates. A competition between elongation and depolymerization rates yields different equilibrium masses of fibril at different shear rates. The model results agree quantitatively well with experimental data on the rate of aggregation and mass of fibrils as a function of shear rate. The modeling framework can be used to explain the shear rate-dependent aggregation of other amyloidogenic proteins.
淀粉样蛋白β（Aβ40）是一类已知的淀粉样蛋白，会聚集形成纤维状网络。聚集速度和纤维产量对外部能量输入（如剪切力）很敏感。在这项工作中，分别使用科特（Couette）细胞和轨道摇床对 Aβ40 溶液进行简单剪切和振动实验。实验表明，在均匀剪切下，纤维的质量和聚集速率都随剪切速率的增加而增加。在轨道振动的情况下，滞后时间随摇床的转速降低，但所有搅拌速度下的最终纤维质量相同。为了解释这种聚集动力学的对比行为，开发了一个种群平衡模型来解释剪切对 Aβ聚集的影响。该动力学模型包括初级成核、次级成核、伸长、断裂和解聚步骤。稳态均匀剪切的影响编码在解聚速率常数（k）中，结果表明 k 最初随剪切速率降低，然后在高剪切速率下饱和。伸长率和解聚率之间的竞争导致在不同的剪切速率下具有不同的纤维平衡质量。模型结果与聚合速率和纤维质量作为剪切速率函数的实验数据定量吻合。该建模框架可用于解释其他淀粉样蛋白的剪切速率依赖性聚集。
