Spatial self-organization of enzymes in complex reaction networks

Abstract

Living systems contain intricate biochemical networks whose structure is closely related to their function and allows them to exhibit robust behavior in the presence of external stimuli. Such networks typically involve catalytic enzymes, which can have non-trivial transport properties, in particular chemotaxis-like directed motion along gradients of substrates and products. Here, we find that taking into account enzyme chemotaxis in models of catalyzed reaction networks can lead to their spatial self-organization in a process similar to biomolecular condensate formation. We develop a general theory for arbitrary reaction networks, and systematically study all closed unimolecular reaction networks involving up to six chemicals. Importantly, we find that network-wide propagation of concentration perturbations can be key to enabling self-organization. The ability to self-organize is highly dependent on the relative signs of the chemotactic mobilities of the enzymes to their substrate and product and on the global network structure. We find that spontaneous self-organization through chemotaxis can provide an avenue for the self-regulation of metabolic activity in complex catalyzed reaction networks. The network-induced interaction mechanism we uncover operates in the regime where the substrate molecules are diffusion-limited, suggesting that signaling molecules could take advantage of this scenario towards their functionality.