Quasi-steady state (QSS) reduction is a commonly used method to lower the dimension of a differential equation model of a chemical reaction network. From a mathematical perspective, QSS reduction is generally interpreted as a special type of singular perturbation reduction, but in many instances the correspondence is not worked out rigorously, and the QSS reduction may yield incorrect results. The present paper contains a thorough discussion of QSS reduction and its relation to singular perturbation reduction for the special, but important, case when the right hand side of the differential equation is linear in the variables to be eliminated. For this class we give necessary and sufficient conditions for a singular perturbation reduction (in the sense of Tikhonov and Fenichel) to exist, and to agree with QSS reduction. We then apply the general results to chemical reaction networks with non-interacting species, generalizing earlier results and methods for steady states to quasi-steady state scenarios. We provide easy-to-check graphical conditions to select parameter values yielding to singular perturbation reductions and additionally, we identify a choice of parameters for which the corresponding singular perturbation reduction agrees with the QSS reduction. Finally we consider a number of examples.
For a 2-D coupled PDE-ODE bulk-cell model, we investigate symmetry-breaking bifurcations that can emerge when two bulk diffusing species are coupled to two-component nonlinear intracellular reactions that are restricted to occur only within a disjoint collection of small circular compartments, or "cells", of a common small radius that are confined in a bounded 2-D domain. Outside of the union of these cells, the two bulk species with comparable diffusivities and bulk degradation rates diffuse and globally couple the spatially segregated intracellular reactions through Robin boundary conditions…
A reaction system exhibits "absolute concentration robustness" (ACR) in some species if the positive steady-state value of that species does not depend on initial conditions. Mathematically, this means that the positive part of the variety of the steady-state ideal lies entirely in a hyperplane of the form $x_i=c$, for some $c>0$. Deciding whether a given reaction system -- or those arising from some reaction network -- exhibits ACR is difficult in general, but here we show that for many simple networks, assessing ACR is straightforward. Indeed, our criteria for ACR can be performed by simply …
We mathematically model the uptake of phosphorus by a soil community consisting of a plant and two bacterial groups: copiotrophs and oligotrophs. Four equilibrium states emerge, one for each of the species monopolising the resource and dominating the community and one with coexistence of all species. We show that the dynamics are controlled by the ratio of chemical adsorption to bacterial death permitting either oscillatory states or quasi-steady uptake. We show how a steady state can emerge which has soil and plant nutrient content unresponsive to increased fertilization. However, the additio…
The quasi-steady-state approximation is widely used to develop simplified deterministic or stochastic models of enzyme catalyzed reactions. In deterministic models, the quasi-steady-state approximation can be mathematically justified from singular perturbation theory. For several closed enzymatic reactions, the homologous extension of the quasi-steady-state approximation to the stochastic regime, known as the stochastic quasi-steady-state approximation, has been shown to be accurate under the analogous conditions that permit the quasi-steady-state reduction of the deterministic counterpart. Ho…
In this work, we revisit the scaling analysis and commonly accepted conditions for the validity of the standard, reverse and total quasi-steady-state approximations through the lens of dimensional Tikhonov-Fenichel parameters and their respective critical manifolds. By combining Tikhonov-Fenichel parameters with scaling analysis and energy methods, we derive improved upper bounds on the approximation error for the standard, reverse and total quasi-steady-state approximations. Furthermore, previous analyses suggest that the reverse quasi-steady-state approximation is only valid when initial enz…
We study the multistationarity for the reaction networks with one-dimensional stoichiometric subspaces, and we focus on the networks admitting finitely many positive steady states. We prove that if a network admits multistationarity, then network has an embedded one-species network with arrow diagram (->,<-) and another with arrow diagram (<-,->). The inverse is also true if there exist two reactions in the network such that the subnetwork consisting of the two reactions admits at least one and finitely many positive steady states. We also prove that if a network admits at least three positive…
The conditions for the validity of the standard quasi-steady-state approximation in the Michaelis--Menten mechanism in a closed reaction vessel have been well studied, but much less so the conditions for the validity of this approximation for the system with substrate inflow. We analyze quasi-steady-state scenarios for the open system attributable to singular perturbations, as well as less restrictive conditions. For both settings we obtain distinguished invariant slow manifolds and time scale estimates, and we highlight the special role of singular perturbation parameters in higher order appr…
For classic Lotka-Volterra systems governing many interacting species, we establish an exclusion principle that rules out the existence of linearly asymptotically stable steady states in subcommunitites of communities that admit a stable state which is internally D-stable. This type of stability is known to be ensured, e.g., by diagonal dominance or Volterra-Lyapunov stability conditions. By consequence, the number of stable steady states of this type is bounded by Sperner's lemma on anti-chains in a poset. The number of stable steady states can nevertheless be very large if there are many gro…
We solve a conjecture on multiple nondegenerate steady states, and prove bistability for sequestration networks. More specifically, we prove that for any odd number of species, and for any production factor, the fully open extension of a sequestration network admits three nondegenerate positive steady states, two of which are locally asymptotically stable. In addition, we provide a non-empty open set in the parameter space where a sequestration network admits bistability.
The asymmetric simple exclusion process (ASEP) is a model of particle transport used in the study of biological processes such as mRNA translation. In 2014, Zhao and Krishnan introduced a new approach for analyzing the ASEP using probabilistic Boolean networks (PBN). In this paper, we revisit and further explore the PBN approach, with focus on computing steady state distributions. Explicit forms of the structure matrices of some common transitions are obtained. In addition, we derive a simplified method for computing the structure matrices of Boolean functions and a general method for writing …
The estimation of the kinetic parameters requires the careful design of experiments under a constrained set of conditions. Many estimates reported in the literature incorporate protocols that leverage simplified mathematical models known as quasi-steady-state reductions. Such reductions often - but not always - emerge as the result of a singular perturbation scenario. However, the utilization of the singular perturbation reduction method requires knowledge of a dimensionless parameter, $\varepsilon$, that is proportional to the ratio of the reaction's fast and slow timescales. Using techniques…
In this paper, we consider a resource-consumer model taking into account a mutation effect between species (with constant mutation rate). The corresponding mutation operator is a discretization of the Laplacian in such a way that the resulting dynamical system can be viewed as a regular perturbation of the classical chemostat system. We prove the existence of a unique locally stable steady-state for every value of the mutation rate and every value of the dilution rate not exceeding a critical value. In addition, we give an expansion of the steady-state in terms of the mutation rate and we prov…
