Transient amplification limits noise suppression in biochemical networks

Cell physiology is orchestrated, on a molecular level, through complex networks of biochemical reactions. The propagation of random fluctuations through these networks can significantly impact cell behavior, raising challenging questions about how network design shapes the cell's ability to suppress or exploit these fluctuations. Here, drawing on insights from statistical physics, fluid dynamics, and systems biology, we explore how transient amplification phenomena arising from network connectivity naturally limit a biochemical system's ability to suppress small fluctuations around steady-state behaviors. We find that even a simple system consisting of two variables linked by a single interaction is capable of amplifying small fluctuations orders of magnitude beyond the levels predicted by linear stability theory. We also find that adding additional interactions can promote further amplification, even when these interactions implement classic design strategies known to suppress fluctuations. These results establish that transient amplification is an essential factor determining baseline noise levels in stable intracellular networks. Significantly, our analysis is not bound to specific systems or interaction mechanisms: we find that noise amplification is an emergent phenomenon found near steady states in any network containing sufficiently strong interactions, regardless of its form or function.