2025/11/13 by D. Evan Piephoff, Piephoff, D. Evan, Jianshu Cao +1
Biochemistry, Genetics and Molecular Biology · Physics and Astronomy · #Advanced Thermodynamics and Statistical Mechanics #Biological Physics (physics.bio-ph) #Chemical Physics (physics.chem-ph) #FOS: Biological sciences #FOS: Physical sciences #Gene Regulatory Network Analysis #Molecular Networks (q-bio.MN) #Statistical Mechanics (cond-mat.stat-mech) #stochastic dynamics and bifurcation
paper · pdf · doi:10.48550/arxiv.2511.10337
openalex publication_date 2025/11/13 · openalex created_date 2025/11/15 · openalex updated_date 2026/07/28
We examine a biomolecular machine involving a driven, observable process coupled to a hidden process in a kinetically cooperative manner. A stochastic thermodynamics framework is employed to analyze a fluctuation theorem for the first-passage time of the observable process under nonequilibrium steady-state conditions. Based on a generic kinetic model, we demonstrate that, along first-passage trajectories, entropy production remains constant when the changes in stochastic entropy and free energy of the machine are balanced, which corresponds to zero net hidden flux through the initial state manifold. Under this condition, which we define quite generally, this first-passage time fluctuation theorem can be established, with its violation serving as an experimentally detectable signature of hidden detailed balance breaking (which we subsequently characterize). In addition, using an enzymatic model, we show that the violation of our first-passage time fluctuation theorem can be thought of as a consequence of the breakdown of local detailed balance in the steps linking coarse-grained states that correspond to the initial and intermediate state manifolds. In the absence of hidden current, the fluctuation theorem is restored, and a mesoscopic local detailed balance condition can be established, which has implications for the thermodynamic analysis of driven, coarse-grained systems. This work sheds significant light on the unique connections between stochastic thermodynamic quantities and kinetic measurements in complex cooperative networks.