Modular Design of Artificial Tissue Homeostasis: Robust Control through Synthetic Cellular Heterogeneity
Figure 6
Parametric optimization of the UPC module.
(A) GA optimization progress for three representative generations, using an ODE model of the UPC module. The GA objective function is a three-component step-function, with zero UPC activity below a defined threshold, an ignored transition region, and high activity above the transition region. (B) Gillespie simulations of System 3, corresponding to optimization progress in A. (C) Average UPC module transfer curves when the reverse response is either excluded or included in the subnetwork GA optimization. (D) Full system behavior corresponding by row to the module optimization results in C. (E) Distribution of rate constants for the optimized parameter vectors determined by 75 independent GA runs of 1000 generations each, using both forward and reverse response objective functions. (F) Clustered sensitivity analysis of the UPC Module. Each column corresponds to a “parameter sensitivity signature” for each of the 75 local parameter neighborhoods that we sampled; rows correspond to the analyzed parameters of the UPC module. First-order sensitivity values shown in the heat map range from 0.0 (black) to 0.5 (red).