Search for: All records

Abstract We analyze the static response to kinetic perturbations of nonequilibrium steady states that can be modeled as diffusions. We demonstrate that kinetic response is purely a nonequilibirum effect, measuring the degree to which the Fluctuation-Dissipation Theorem is violated out of equilibrium. For driven diffusions in a flat landscape, we further demonstrate that such response is constrained by the strength of the nonequilibrium driving via quantitative inequalities. 

Abstract Living things benefit from exquisite molecular sensitivity in many of their key processes, including DNA replication, transcription and translation, chemical sensing, and morphogenesis. At thermodynamic equilibrium, the basic biophysical mechanism for sensitivity is cooperative binding, for which it can be shown that the Hill coefficient, a sensitivity measure, cannot exceed the number of binding sites. Generalizing this fact, we find that for any kinetic scheme, at or away from thermodynamic equilibrium, a very simple structural quantity, the size of the support of a perturbation, always limits the effective Hill coefficient. We show how this bound sheds light on and unifies diverse sensitivity mechanisms, including kinetic proofreading and a nonequilibrium Monod-Wyman-Changeux (MWC) model proposed for theE. coliflagellar motor switch, representing in each case a simple, precise bridge between experimental observations and the models we write down. In pursuit of mechanisms that saturate the support bound, we find a nonequilibrium binding mechanism, nested hysteresis, with sensitivity exponential in the number of binding sites, with implications for our understanding of models of gene regulation and the function of biomolecular condensates. 

Abstract We propose and investigate a method for identifying timescales of dissipation in nonequilibrium steady states modeled as discrete-state Markov jump processes. The method is based on how the irreversibility—measured by the statistical breaking of time-reversal symmetry—varies under temporal coarse-graining. We observe a sigmoidal-like shape of the irreversibility as a function of the coarse-graining time whose functional form we derive for systems with a fast driven transition. This theoretical prediction allows us to develop a method for estimating the dissipative time scale from time-series data by fitting estimates of the irreversibility to our predicted functional form. We further analyze the accuracy and statistical fluctuations of this estimate. 

We study the response of chemical reaction networks driven far from equilibrium to logarithmic perturbations of reaction rates. The response of the mean number of a chemical species is observed to be quantitively limited by number fluctuations and the maximum thermodynamic driving force. We prove these trade-offs for linear chemical reaction networks and a class of nonlinear chemical reaction networks with a single chemical species. Numerical results for several model systems support the conclusion that these trade-offs continue to hold for a broad class of chemical reaction networks, though their precise form appears to sensitively depend on the deficiency of the network.