PT  - JOURNAL ARTICLE
AU  - Michaëlle N. Mayalu
AU  - Richard M. Murray
TI  - Theoretical Design of Paradoxical Signaling-Based Synthetic Population Control Circuit in <em>E. coli</em>
AID  - 10.1101/2020.01.27.921734
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.27.921734
4099  - http://biorxiv.org/content/early/2020/01/28/2020.01.27.921734.short
4100  - http://biorxiv.org/content/early/2020/01/28/2020.01.27.921734.full
AB  - We have developed a mathematical framework to analyze the cooperative control of cell population homeostasis via paradoxical signaling in synthetic contexts. Paradoxical signaling functions through quorum sensing (where cells produce and release a chemical signal as a function of cell density). Precisely, the same quorum sensing signal provides both positive (proliferation) and negative (death) feedback in different signal concentration regimes. As a consequence, the relationship between intercellular quorum sensing signal concentration and net growth rate (cell proliferation minus death rates) can be non-monotonic. This relationship is a condition for robustness to certain cell mutational overgrowths and allows for increased stability in the presence of environmental perturbations. Here, we explore stability and robustness of a conceptualized synthetic circuit. Furthermore, we asses possible design principles that could exist among a subset of paradoxical circuit implementations. This analysis sparks the development a bio-molecular control theory to identify ideal underlying characteristics for paradoxical signaling control systems.