Selective Control of the Apoptosis Signaling Network in Heterogeneous Cell Populations

Abstract

We have explored two methods for the study of selectivity in cell populations. The first is an exhaustive search method limited to three node perturbations. The second is an effective linear model, based on interpolation of single node sensitivity, in which the selective combinations can be found by linear programming optimization. We found that selectivity is promoted by acting on the least sensitive nodes in the case of weak populations, while selective control of robust populations is optimized through perturbations of more sensitive nodes. High throughput experiments with heterogeneous cell lines could be designed in an analogous manner, with the further possibility of incorporating the selectivity optimization process into a closed-loop control system.