KINECTICS OF PROTEIN- AGGREGATION AND SELF ASSEMBLY

Abstract

The process of protein aggregation is a vital one which depends on time and necessitates models which transcend closed-system approaches to become models of dynamic kinetics and proteostasis. The generalized modelling approach connects the physical mechanism of aggregation with the biological system of aging. This physical model is composed of kinetic laws, the behaviours of the source terms (monomer generation/elimination), and thermos- reversible assembly. The model predicts the scaling behaviours of aggregation which depend on whether the process is limited by the formation of aggregates or the generation of monomers. The biological aspect of the modelling framework takes into account the effect of the decline in the process of proteostasis in a systems biology model. Coupled differential equations form the basis of this biological model with consideration of the decline in physiological function, hormone regulation, genetic instability, and gender-related effects. Importantly, the non-linear dynamics of proteostasis with respect to age-related stresses and inefficient clearing must be accounted for since they can lead to a tipping point where a rapid build-up occurs.