Homeostatic controllers compensating for growth and perturbations.

Area of Science:

• Molecular Biology
• Synthetic Biology
• Systems Biology

Background:

• Cells and organisms utilize homeostatic mechanisms to adapt to environmental changes.
• The interplay between cellular growth and homeostasis is crucial for molecular and synthetic biology.
• Understanding control circuits that counteract growth-induced dilution is of increasing interest.

Purpose of the Study:

• To evaluate the performance of negative feedback controllers under various growth laws and perturbations.
• To identify optimal controller designs for maintaining homeostasis during cell growth.
• To provide insights into designing robust biological control circuits.

Main Methods:

• Deterministic mass action kinetics were employed, assuming instantaneous mixing of cell content.
• Simulations were performed for controllers responding to different growth laws (surface-to-volume, linear, exponential).
• Controller performance was assessed against step-wise perturbations in volume and a controlled compound.

Main Results:

• All simulated controllers ideally returned the controlled variable to its set-point after perturbations.
• Derepression kinetics and autocatalytic integral control demonstrated superior performance in defending against growth and perturbations.
• Autocatalytic controllers exhibited a slight offset from the theoretical set-point.

Conclusions:

• Controller performance is influenced by the kinetic implementation of integral control and negative feedback loop structure.
• Negative feedback structures with repression/derepression steps can enhance controller performance.
• The findings offer guidance for designing biological feedback systems to counter dilution effects during growth.