Topologically constrained fluctuations and thermodynamics regulate nonequilibrium response

The limits on a system's response to external perturbations inform our understanding of how physical properties can be shaped by microscopic characteristics. Here, we derive constraints on the steady-state nonequilibrium response of physical observables in terms of the topology of the microscopic state space and the strength of thermodynamic driving. Notably, evaluation of these limits requires no kinetic information beyond the state-space structure. When applied to models of receptor binding, we find that sensitivity is bounded by the steepness of a Hill function with a Hill coefficient enhanced by the chemical driving beyond the structural equilibrium limit.