Modulating Biological Rhythms: A Noncomputational Strategy Harnessing Nonlinearity and Decoupling Frequency and Amplitude.

Understanding and achieving concurrent modulation of amplitude and frequency, particularly adjusting one quantity and simultaneously sustaining the other at an invariant level, are of paramount importance for complex biophysical systems, including the signal pathway where different frequency indicates different upstream signal yielding a certain downstream physiological function while different amplitude further determines different efficacy of a downstream output. However, such modulators with clearly described and universally valid mechanisms are still lacking. Here, we rigorously propose an easy-to-use control strategy containing only one or two steps, leveraging the nonlinearity in the modulated systems to decouple frequency and amplitude in a noncomputational manner. The strategy's efficacy is demonstrated using representative biochemical systems and, thus, it could be potentially applicable to modulating rhythms in experiments of biochemistry and synthetic biology.