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In silico analysis of metabolic burden effects on a multicellular integral controller

Campanile, G.; Martinelli, V.; Salzano, D.; Fiore, D.; di Bernardo, M.

2025-04-16 synthetic biology
10.1101/2024.11.12.623154 bioRxiv
Show abstract

Metabolic burden is a critical limiting factor in the design of synthetic circuits, affecting both their reliability and performance. To mitigate its effects, distributing control functions across different cell populations within a multicellular control architecture offers a promising solution, while simultaneously enhancing modularity and re-usability of the circuits. We first present a model that explicitly accounts for limited ribosome availability within cells. Using this framework, we then derive a mathematical model of a multicellular antithetic integral controller that incorporates these shared resources. Through numerical bifurcation analysis and in silico agent-based experiments in BSim, we compare the multicellular controller against its traditional single-cell (embedded) implementation, evaluating both resource utilization and stability.

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