Designing Robustness to Temperature in a Feedforward Loop Circuit

Abstract

'Incoherent feedforward loops' represent important biomolecular circuit elements capable of a rich set of dynamic behavior including adaptation and pulsed responses. Temperature can modulate some of these properties through its effect on the underlying reaction rate parameters. It is generally unclear how to design a circuit where these properties are robust to variations in temperature. Here, we address this issue using a combination of tools from control and dynamical systems theory as well as preliminary experimental measurements towards such a design. Using a structured uncertainty representation, we analyze a standard incoherent feedforward loop circuit, noting mechanisms that intrinsically confer temperature robustness to some of its properties. Further, we study design variants that can enhance this robustness to temperature, including different negative feedback configurations as well as conditions for perfect temperature compensation. Finally, we find that the response of an incoherent feedforward loop circuit in cells can change with temperature. These results present groundwork for the design of a temperature-robust incoherent feedforward loop circuit.