Effective connectivity determines the critical dynamics of biochemical networks

Abstract

Living systems comprise interacting biochemical components in very large networks. Given their high connectivity, biochemical dynamics are surprisingly not chaotic but quite robust to perturbations—a feature C.H. Waddington named canalization. Because organisms are also flexible enough to evolve, they arguably operate in acriticaldynamical regime between order and chaos. The established theory of criticality is based on networks of interacting automata where Boolean truth values model presence/absence of biochemical molecules. The dynamical regime is predicted using network connectivity and node bias (to be on/off) as tuning parameters. Revising this to account for canalization leads to a significant improvement in dynamical regime prediction. The revision is based oneffective connectivity, a measure of dynamical redundancy that buffers automata response to some inputs. In both random and experimentally validated systems biology networks, reducing effective connectivity makes living systems operate in stable or critical regimes even though the structure of their biochemical interaction networks predicts them to be chaotic. This suggests that dynamical redundancy may be naturally selected to maintain living systems near critical dynamics, providing both robustness and evolvability. By identifying how dynamics propagates preferably via effective pathways, our approach helps to identify precise ways to design and control network models of biochemical regulation and signalling.