Biological systems operate far from thermodynamic equilibrium through the continuous consumption of energy. Their functions emerge collectively from interactions among many constituents, such as cells in tissues, bacteria in biofilms, or biomolecules in the cell nucleoplasm. Understanding the physical principles governing these systems requires a predictive framework of non-equilibrium statistical physics that can describe both their steady states and dynamics. Such a framework can explain and predict emergent phenomena, including phase separation, collective transport and entropy production. Our research addresses these questions through the following projects.
Hydrodynamics and Phase Transitions in Cellular Aggregates
Multicellular aggregates are intermediate biological systems between single cells and tissues or organs. Often engineered as organoids or spheroids, they provide tractable models to study development, disease, drug response, and cancer progression.
Active dipole-like cell–cell (attraction) and cell–substrate (motility) interactions are widely recognized as key mechanisms driving the formation of dense multicellular aggregates. The interplay between the attraction and motility leads to a rich spectrum of collective behaviors, including re-entrant phase transitions, complex phase coexistence and slowdown of transports.
We propose an analytically tractable model inspired by colony-forming N. gonorrhoeae bacteria as a representative example of active cellular aggregates. We develop a two-dimensional fluctuating hydrodynamics framework based on microscopic dynamics and study how transport properties, particularly diffusivity and conductivity, are suppressed during colony formation.
At long times, the competition between motility and attractive interactions leads to two distinct dense phases separated by a homogeneous state. By varying control parameters such as particle density, force turnover time, and attraction strength, we find that these phases arise through two fundamentally different types of phase transitions. Motility-driven clustering is continuous, characterized by large fluctuations and high sensitivity to perturbations, and may facilitate early exploratory aggregation in uncertain environments. In contrast, attraction-driven clustering is first-order, involving metastability and hysteresis, which can enhance stability and may explain the robustness of mature aggregates and biofilms.
Active Microemulsions in the Cell Nucleus
Transcription is the first and essential step of gene expression, during which the genetic information encoded in DNA is copied into messenger RNA (mRNA). The transcriptional activity of RNA polymerase drives microphase separation between RNA-rich and DNA-rich regions in the cell nucleus. In this process, polymerase molecules exhibit a behavior analogous to amphiphiles in a conventional oil-and-water emulsion by interacting with both DNA and RNA. Unlike passive amphiphiles, however, the amphiphilic nature of polymerase enzymes is maintained by continuous energy consumption and is therefore intrinsically out of equilibrium. This active behavior can profoundly influence the structure, stability, and relaxation dynamics of nuclear microemulsions, making them inaccessible to existing equilibrium theories.
To understand these phenomena, we develop a lattice-based model of active microemulsions in which amphiphiles undergo non-equilibrium switching between different states. Starting from the microscopic dynamics, we systematically coarse-grain the model to derive continuum equations that describe the large-scale behavior of the system. The resulting theory allows us to characterize static and dynamic structure factors and entropy production, providing a quantitative framework for understanding active microemulsions. Our approach is directly relevant to experiments probing the structural organization and relaxation dynamics of chromatin and other nuclear components during transcription.
Some References
- Density-dependent transport coefficients in two-dimensional cellular aggregates
S Chakraborti and V Zaburdaev
Physical Review E 112 (3), 034406 (2025) - Transport in cellular aggregates described by fluctuating hydrodynamics
S Chakraborti and V Zaburdaev
Physical Review Research 6 (4), 043064 (2024) - Nonequilibrium Structure and Relaxation in Active Microemulsions
R Chatterjee, HS Kuan, F Jülicher and V Zaburdaev
Physical Review Letters 135 (3), 038401 (2025)