Balancing Cell Populations Endowed with a Synthetic Toggle Switch via Adaptive Pulsatile Feedback Control

Area of Science:

• Synthetic Biology
• Control Theory
• Computational Biology

Background:

• Controlling cells with genetic toggle switches is a key challenge in synthetic biology.
• Existing periodic forcing methods lack robustness against biological system uncertainties and stochasticity.
• Balancing cell populations in an undifferentiated state is crucial for many synthetic biology applications.

Purpose of the Study:

• To develop robust feedback control strategies for managing genetic toggle switches.
• To enhance the performance and stability of cell population balancing.
• To investigate the effectiveness of real-time control of pulsatile inputs.

Main Methods:

• Development and simulation of feedback control algorithms.
• Agent-based modeling to simulate cellular behavior under uncertainty.
• In silico experiments to test control strategies against stochastic effects, cell growth, and inducer diffusion.

Main Results:

• Feedback control significantly enhances robustness and stability of population balancing.
• The proposed strategies maintain population coherence, confirming previous findings.
• Demonstrated effectiveness even with biological noise, cell growth, and diffusion.

Conclusions:

• Feedback control offers a robust and stable solution for managing genetic toggle switches.
• This approach overcomes limitations of non-feedback methods in realistic biological conditions.
• Provides insights into practical in vivo implementation by comparing different control solutions.