Evaluation of Protein Regulatory Kinetics Schemes in Perturbed Cell Growth Environments by Using Sensitivity Methods

G. Maria

Abstract
Homeostatic regulatory mechanisms are developed to study the recovering characteristics of the cell components to their steady-states after being perturbed. Such simplified kinetic mechanisms mimic the balanced cell-growth via quasi-invariant cell-component's levels, despite continuous volume growing diluting effects and perturbations in the environment. Recently, Sewell et al.1 proposed nine kinetic schemes to regulate a generic protein P, based on a limited number of reactions. Nominal steady-state (QSS) concentrations of the protein and their encoding gene and maximum regulatory effectiveness constraints allowed ranking the kinetic schemes according to their stationary effectiveness. Yang et al.2 extended this analysis by applying a maximum recovering rate objective function to estimate the rate constants. In the present study, a sensitivity-stability-based analysis of the QSS complete the previous investigations of regulatory models, by accounting the QSS-response surface to stationary perturbations in the P synthesis/dilution rate, characterisation of the QSS quality, sensitivity and local stability, and approaching a multi-criteria ranking of regulatory mechanisms.

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Keywords
Protein and gene regulatory kinetic models, cell regulatory module design, sensitivity and stability analysis