Negative Feedback Facilitates Temperature Robustness in Biomolecular Circuit Dynamics

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Shaunak Sen and Richard M. Murray
Submitted, Synthetic Biology: Engineering, Evolution and Design (SEED)

Temporal dynamics in many biomolecular circuits can change with temperature because of the temperature dependence of underlying reaction rate parameters. It is generally unclear what circuit mechanisms can inherently facilitate robustness in the dynamics to variations in temperature. Here, we address this issue using a combination of mathematical models and experimental measure- ments in a cell-free transcription-translation system. We find that negative transcriptional feedback can reduce the e↵ect of temperature variation on circuit dynamics. Further, we find that effective negative feedback due to first-order degradation mechanisms can also enable such a temperature robustness effect. Finally, we estimate temperature dependence of key parameters mediating such negative feedback mechanisms. These results should be useful in the design of temperature robust circuit dynamics.