465683 Computational Modeling of Amyloid Aggregation Kinetics
The process of amyloid formation involves a two-step pattern of initial nucleation corresponding to a lag phase followed by a fiber elongation phase. This behavior has been modeled empirically using mathematical functions such as the logistic function, and other kinetic models, such as the Finke-Watzky (F-W) 2-step mechanism, which capture the near sigmoidal shape of the aggregation curve. However, experimental aggregation data does not always mirror the simple S-shape of a sigmoidal function. In this work we have developed a model for amyloid aggregation kinetics following a nucleation, elongation and fragmentation scheme. The effect of factors influencing aggregation kinetics is studied by changing parameters, such as fragmentation rate, initial concentrations of seeds, or critical nucleus size. Our results show that non-sigmoidal aggregation kinetics can result from varying some of the above mentioned parameters.
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