Abstract. In this paper we examine matrices which arise naturally as Jacobians in chemical dynamics. We are particularly interested in when these Jacobians are P matrices (up to a sign change), ensuring certain bounds on their eigenvalues, precluding certain behaviour such as multiple equilibria, and sometimes implying stability. We first explore reaction systems and derive results which provide a deep connection between system structure and the P matrix property. We then examine a class of systems consisting of reactions coupled to an external rate-dependent negative feedback process, and characterise conditions which ensure the P matrix property survives the negative feedback. The techniques presented are applied to examples published in the mathematical and biological literature.

Reference implementation: reaction-networks.net/control/. Source code and binaries, released under the GPLv3: reaction-networks.net/control/download/. Documentation: reaction-networks.net/wiki/CoNtRol.

Abstract. A class of chemical reaction networks is described with the property that each positive equilibrium is locally asymptotically stable relative to its stoichiometry class, an invariant subspace on which it lies. The reaction systems treated are characterised primarily by the existence of a certain factorisation of their stoichiometric matrix, and strong connectedness of an associated graph. Only very mild assumptions are made about the rates of reactions, and in particular, mass action kinetics are not assumed. In many cases, local asymptotic stability can be extended to global asymptotic stability of each positive equilibrium relative to its stoichiometry class. The results are proved via the construction of Lyapunov functions whose existence follows from the fact that the reaction networks define monotone dynamical systems with increasing integrals.

We introduce a mixed-integer linear programming (MILP) framework capable of determining whether a chemical reaction network possesses the property of being endotactic or strongly endotactic. The network property of being strongly endotactic is known to lead to persistence and permanence of chemical species under genetic kinetic assumptions, while the same result is conjectured but as yet unproved for general endotactic networks. The algorithms we present are the first capable of verifying endotacticity of chemical reaction networks for systems with greater than two constituent species. We implement the algorithms in the open-source online package CoNtRol and apply them to several well-studied biochemical examples, including the general n-site phosphorylation / dephosphorylation networks and a circadian clock mechanism.

We introduce and analyse a simple model for two non-excitable cells that are dynamically coupled by a gap junction, a plaque of aqueous channels that electrically couple the cells. The gap junction channels have a low and high conductance state, and the transition rates between these states are voltage-dependent. We show that the number and stability of steady states of the system has a simple relationship with the determinant of the Jacobian matrix. For the case that channel opening rates decrease with increasing trans-junctional voltage, and closing rates increase with increasing trans-junctional voltage, we show that the system is monotone, with tridiagonal Jacobian matrix, and hence every initial condition evolves to a steady state, but that there may be multiple steady states.

In this paper, we use a variety of mathematical techniques to explore existence, local stability, and global stability of equilibria in abstract models of mitochondrial metabolism. The class of models constructed is defined by the biological description of the system, with minimal mathematical assumptions. The key features are an electron transport chain coupled to a process of charge translocation across a membrane. In the absence of charge translocation these models have previously been shown to behave in a very simple manner with a single, globally stable equilibrium. We show that with charge translocation the conclusion about a unique equilibrium remains true, but local and global stability do not necessarily follow. In sufficiently low dimensions -i.e. for short electron transport chains -it is possible to make claims about local and global stability of the equilibrium. On the other hand, for longer chains, these general claims are no longer valid. Some particular conditions which ensure stability of the equilibrium for chains of arbitrary length are presented.

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