Stoichiometric recipes for periodic oscillations in reaction networks

Abstract: Oscillatory chemical reactions are functional components in a variety of biological contexts. In chemistry, the construction and identification of even rudimentary oscillators remain elusive and lack a general framework. Using parameter-rich kinetics - a methodology enabling the disentanglement of parametric dependencies from structural analysis - we investigate the stoichiometry of chemical oscillators. We introduce the concept of oscillatory cores - minimal subnetworks that guarantee the potential for oscillations in any reaction network containing them. These cores fall into two classes, depending on whether they involve positive or negative feedback. In particular, the latter class unveils a family of oscillators - yet to be synthesized - that require a minimum number of reaction steps to exhibit oscillations, a phenomenon we refer to as the principle of length. We identify several mechanisms through which catalysis promotes oscillations: (I) furnishing instability (e.g. autocatalysis), (II) lifting dependencies, (III) lowering length thresholds. Notwithstanding this mechanistic ubiquity, we show that oscillators can also be realized without employing any catalysis. Our results highlight branches of chemistry where oscillators are likely to arise by chance, suggest new strategies for their design, and point to novel classes of oscillators yet to be realized experimentally.