Dynamic Analysis and Robust Strategy for the Delayed Paradoxical Cell Population Control Circuit.

Area of Science:

• Synthetic biology
• Systems biology
• Biochemical engineering

Background:

• Synthetic paradoxical control circuits are employed for regulating cell population density.
• Time delays and paradoxical interactions within these circuits can complicate stable population control by affecting system dynamics.

Purpose of the Study:

• To propose a robust strategy for cell population control in delayed paradoxical circuits.
• To analyze bistable switching and oscillatory behaviors to achieve stable population regulation.

Main Methods:

• Identification of five distinct population outcomes and their stabilization criteria.
• Analysis of bistable switching mechanisms influenced by initial cell density and time delays.
• Investigation of Hopf bifurcation leading to oscillations due to time delays.

Main Results:

• Two bistable switching mechanisms were identified, dependent on initial cell density and blasticidin-induced cell death time delay.
• Time delays were shown to induce periodic oscillations via Hopf bifurcation, destabilizing effective control.
• Oscillations can be mitigated by adjusting blasticidin concentration.

Conclusions:

• A robust control strategy involving regulation of initial cell population density and blasticidin concentration is proposed.
• Findings advance the design of robust population control circuits for synthetic biology and cell therapy.
• Understanding bistability and oscillations is crucial for stable control in delayed synthetic circuits.