Multi-Scale Fluctuations in Non-Equilibrium Systems: Statistical Physics and Biological Application

Understanding how fluctuations continuously propagate across spatial scales is fundamental for our understanding of inanimate matter. This is exemplified by self-similar fluctuations in critical phenomena and the propagation of energy fluctuations described by the Kolmogorov-Law in turbulence. Our understanding is based on powerful theoretical frameworks that integrate fluctuations on intermediary scales, as in renormalisation group or coupled mode theory. In striking contrast to typical inanimate systems, living matter is typically organised into a hierarchy of processes on a discrete set of spatial scales: from biochemical processes embedded in dynamic subcellular compartments to cells giving rise to tissues. Therefore, the understanding of living matter requires novel theories that predict the interplay of fluctuations on multiple scales of biological organisation and the ensuing emergent degrees of freedom. In this thesis, we derive a general theory of the multi-scale propagation of fluctuations in non-equilibrium systems and show that such processes underlie the regulation of cellular behaviour. Specifically, we draw on paradigmatic systems comprising stochastic many-particle systems undergoing dynamic compartmentalisation. We first derive a theory for emergent degrees of freedom in open systems, where the total mass is not conserved. We show that the compartment dynamics give rise to the localisation of probability densities in phase space resembling quasi-particle behaviour. This emergent quasi-particle exhibits fundamentally different response kinetics and steady states compared to systems lacking compartment dynamics. In order to investigate a potential biological function of such quasi-particle dynamics, we then apply this theory to the regulation of cell death. We derive a model describing the subcellular processes that regulate cell death and show that the quasi-particle dynamics gives rise to a kinetic low-pass filter which suppresses the response of the cell to fast fluituations in cellular stress signals. We test our predictions experimentally by quantifying cell death in cell cultures subject to stress stimuli varying in strength and duration. In closed systems, where the total mass is conserved, the effect of dynamic compartmentalisation depends on details of the kinetics on the scale of the stochastic many-particle dynamics. Using a second quantisation approach, we derive a commutator relation between the kinetic operators and the change in total entropy. Drawing on this, we show that the compartment dynamics alters the total entropy if the kinetics of the stochastic many-particle dynamics violate detailed balance. We apply this mechanism to the activation of cellular immune responses to RNA-virus infections. We show that dynamic compartmentalisation in closed systems gives rise to giant density fluctuations. This facilitates the emergence of gelation under conditions that violate theoretical gelation criteria in the absence of compartment dynamics. We show that such multi-scale gelation of protein complexes on the membranes of dynamic mitochondria governs the innate immune response. Taken together, we provide a general theory describing the multi-scale propagation of fluctuations in biological systems. Our work pioneers the development of a statistical physics of such systems and highlights emergent degrees of freedom spanning different scales of biological organisation. By demonstrating that cells manipulate how fluctuations propagate across these scales, our work motivates a rethinking of how the behaviour of cells is regulated

Multi-scale fluctuations in non-equilibrium systems: statistical physics and biological application

Understanding how fluctuations continuously propagate across spatial scales is fundamental for our understanding of inanimate matter. This is exemplified by self-similar fluctuations in critical phenomena and the propagation of energy fluctuations described by the Kolmogorov-Law in turbulence. Our understanding is based on powerful theoretical frameworks that integrate fluctuations on intermediary scales, as in renormalisation group or coupled mode theory. In striking contrast to typical inanimate systems, living matter is typically organised into a hierarchy of processes on a discrete set of spatial scales: from biochemical processes embedded in dynamic subcellular compartments to cells giving rise to tissues. Therefore, the understanding of living matter requires novel theories that predict the interplay of fluctuations on multiple scales of biological organisation and the ensuing emergent degrees of freedom. In this thesis, we derive a general theory of the multi-scale propagation of fluctuations in non-equilibrium systems and show that such processes underlie the regulation of cellular behaviour. Specifically, we draw on paradigmatic systems comprising stochastic many-particle systems undergoing dynamic compartmentalisation. We first derive a theory for emergent degrees of freedom in open systems, where the total mass is not conserved. We show that the compartment dynamics give rise to the localisation of probability densities in phase space resembling quasi-particle behaviour. This emergent quasi-particle exhibits fundamentally different response kinetics and steady states compared to systems lacking compartment dynamics. In order to investigate a potential biological function of such quasi-particle dynamics, we then apply this theory to the regulation of cell death. We derive a model describing the subcellular processes that regulate cell death and show that the quasi-particle dynamics gives rise to a kinetic low-pass filter which suppresses the response of the cell to fast fluituations in cellular stress signals. We test our predictions experimentally by quantifying cell death in cell cultures subject to stress stimuli varying in strength and duration. In closed systems, where the total mass is conserved, the effect of dynamic compartmentalisation depends on details of the kinetics on the scale of the stochastic many-particle dynamics. Using a second quantisation approach, we derive a commutator relation between the kinetic operators and the change in total entropy. Drawing on this, we show that the compartment dynamics alters the total entropy if the kinetics of the stochastic many-particle dynamics violate detailed balance. We apply this mechanism to the activation of cellular immune responses to RNA-virus infections. We show that dynamic compartmentalisation in closed systems gives rise to giant density fluctuations. This facilitates the emergence of gelation under conditions that violate theoretical gelation criteria in the absence of compartment dynamics. We show that such multi-scale gelation of protein complexes on the membranes of dynamic mitochondria governs the innate immune response. Taken together, we provide a general theory describing the multi-scale propagation of fluctuations in biological systems. Our work pioneers the development of a statistical physics of such systems and highlights emergent degrees of freedom spanning different scales of biological organisation. By demonstrating that cells manipulate how fluctuations propagate across these scales, our work motivates a rethinking of how the behaviour of cells is regulated

Random Matrix Theory for Stochastic and Quantum Many-Body Systems

Random matrix theory (RMT) is a mathematical framework that has found profound applications in physics, particularly in the study of many-body systems. Its success lies in its ability to predict universal statistical properties of complex systems, independent of the specific details. This thesis explores the application of RMT to two classes of many-body systems: quantum and stochastic many-body systems. Within the quantum framework, this work focuses on the Bose-Hubbard system, which is paradigmatic for modeling ultracold atoms in optical traps. According to RMT and the Eigenstate Thermalization Hypothesis (ETH), eigenstate-to-eigenstate fluctuations of expectation values of local observables decay rapidly with the system size in the thermodynamic limit at sufficiently large temperatures. Here, we study these fluctuations in the classical limit of fixed lattice size and increasing boson number. We find that the fluctuations follow the RMT prediction for large system sizes but deviate substantially for small lattices. Partly motivated by these results, the Bose-Hubbard model on three sites is studied in more detail. On few sites, the Bose-Hubbard model is known to be a mixed system, being neither fully chaotic nor integrable. We compare energy-resolved classical and quantum measures of chaos, which show a strong agreement. Deviations from RMT predictions are attributed to the mixed nature of the few-site model. In the context of stochastic systems, generators of Markov processes are studied. The focus is on the spectrum. We present results from two investigations of Markov spectra. First, we investigate the effect of sparsity on the spectrum of random generators. Dense random matrices previously used as a model for generic generators led to very large spectral gaps and therefore to unphysically short relaxation times. In this work, a model of random generators with adjustable sparsity — number of zero matrix elements — is presented, extending the dense framework. It is shown that sparsity leads to longer, more physically realistic relaxation times. Second, the generator spectrum of the Asymmetric Simple Exclusion Process (ASEP), a quintessential model in non-equilibrium statistical mechanics, is analyzed. We investigate the spectral boundary, which is characterized by pronounced spikes. The emergence of these spikes is analyzed from several points of view, including RMT. The results presented in this thesis contribute to the understanding of the applicability of RMT to many-body systems. This thesis highlights successes such as the explanation of “ETH fluctuations” in Bose-Hubbard models, the improvement of random matrix descriptions by introducing sparsity, and the emergence of spikes in the spectral boundary of the ASEP. The latter is a notable case where RMT provides insights even though the ASEP is a Bethe-integrable system. Furthermore, this thesis shows examples of the limits of RMT, exemplified by the results presented for the Bose-Hubbard model with a few sites

Non-Equilibrium Dynamics of Photoexcited Correlated Quantum Matter

The interaction of time-dependent electromagnetic fields with electrons in quantum materials can give rise to many both fundamentally interesting as well as technologically relevant phenomena like transient band structure manipulations or the emergence of prethermal states of matter, which are not a result of heating. This thesis contributes theoretical insights to both these topics: We model the interference of Floquet and Volkov side bands, which are a result of the dressing of electron states by light, in a time-resolved angle-resolved photoemission spectroscopy (ARPES) experiment. Furthermore, we analyze the emergence of a band-like feature in the non-equilibrium spectral function of a one-dimensional charge-density wave insulator upon periodic driving. Secondly, we use the fermionic truncated Wigner approximation (fTWA), a phase space method for the time evolution of interacting fermions, to study the light-induced order parameter dynamics in SU(N)-symmetric fermionic lattice models. By comparison with exact analytical results for an interaction quench in the Hubbard model, we find that dephasing-induced prethermalization is correctly described by fTWA. We discuss photoinduced prethermal transitions between competing phases of matter in the large-N Hubbard-Heisenberg model and find a pronounced frequency-dependence of the transition. This work contributes to a better understanding of photoinduced order parameter dynamics from a microscopic perspective.2024-01-2