Non-normality Can Facilitate Pulsing in Biomolecular Circuits

Non-normality can underlie pulse dynamics in many engineering contexts. However, its role in pulses generated in biomolecular contexts is generally unclear. Here, we address this issue using the mathematical tools of linear algebra and systems theory on simple computational models of biomolecular circuits. We find that non-normality is present in standard models of feedforward loops. We used a generalized framework and pseudospectrum analysis to identify non-normality in larger biomolecular circuit models, finding that it correlates well with pulsing dynamics. Finally, we illustrate how these methods can be used to provide analytical support to numerical screens for pulsing dynamics as well as provide guidelines for design.