2026
3
Active RNA synthesis patterns nuclear condensates Open access
Andriy Goychuk*; Salman F. Banani*; Pradeep Natarajan*; Ming M. Zheng*; Haoran Wang; Giuseppe Dall’Agnese; Richard A. Young†; Mehran Kardar†; Jonathan E. Henninger†; Arup K. Chakraborty†
* Equal contribution † Corresponding author
In: Cell Systems, vol. 17, pp. 101613, 2026, ISSN: 24054712.
Preprint Repository Abstract Links BibTeX
Finite-Element MethodLiquid-Liquid Phase TransitionNucleolusRNATranscription
In the press
@article{goychuk_active_2026,
title = {Active RNA synthesis patterns nuclear condensates},
author = {Andriy Goychuk and Salman F. Banani and Pradeep Natarajan and Ming M. Zheng and Haoran Wang and Giuseppe Dall’Agnese and Richard A. Young and Mehran Kardar and Jonathan E. Henninger and Arup K. Chakraborty},
doi = {10.1016/j.cels.2026.101613},
issn = {24054712},
year = {2026},
date = {2026-05-01},
urldate = {2026-05-01},
journal = {Cell Systems},
volume = {17},
pages = {101613},
abstract = {Biomolecular condensates are membraneless compartments that organize biochemical processes in cells. In contrast to well-understood mechanisms describing how condensates form and dissolve, the principles underlying condensate patterning—including their size, number, and spacing in the cell—remain largely unknown. We hypothesized that RNA, a key regulator of condensate formation and dissolution, influences condensate patterning. Using nucleolar fibrillar centers (FCs) as a model condensate, we found that inhibiting ribosomal RNA synthesis significantly alters the patterning of FCs. Physical theory and experimental observations support a model whereby active RNA synthesis generates a non-equilibrium state that arrests condensate coarsening and thus contributes to condensate patterning. Altering FC condensate patterning by expression of the FC component treacle ribosome biogenesis factor 1 (TCOF1) impairs ribosomal RNA processing, linking condensate patterning to biological function. These results reveal how non-equilibrium states driven by active chemical processes regulate condensate patterning, which is important for cellular biochemistry and function.},
keywords = {Finite-Element Method, Liquid-Liquid Phase Transition, Nucleolus, RNA, Transcription},
pubstate = {published},
tppubtype = {article}
}
Biomolecular condensates are membraneless compartments that organize biochemical processes in cells. In contrast to well-understood mechanisms describing how condensates form and dissolve, the principles underlying condensate patterning—including their size, number, and spacing in the cell—remain largely unknown. We hypothesized that RNA, a key regulator of condensate formation and dissolution, influences condensate patterning. Using nucleolar fibrillar centers (FCs) as a model condensate, we found that inhibiting ribosomal RNA synthesis significantly alters the patterning of FCs. Physical theory and experimental observations support a model whereby active RNA synthesis generates a non-equilibrium state that arrests condensate coarsening and thus contributes to condensate patterning. Altering FC condensate patterning by expression of the FC component treacle ribosome biogenesis factor 1 (TCOF1) impairs ribosomal RNA processing, linking condensate patterning to biological function. These results reveal how non-equilibrium states driven by active chemical processes regulate condensate patterning, which is important for cellular biochemistry and function.
2024
2
Self-consistent sharp interface theory of active condensate dynamics Open access
Andriy Goychuk†*; Leonardo Demarchi*; Ivan Maryshev; Erwin Frey†
* Equal contribution † Corresponding author
In: Physical Review Research, vol. 6, no. 3, pp. 033082, 2024, ISSN: 2643-1564.
Repository Abstract Links BibTeX
Biomolecular DynamicsEnzymesLiquid-Liquid Phase TransitionNonequilibrium SystemsPattern FormationProtein-Protein InteractionsTraveling Waves
@article{goychuk_self-consistent_2024,
title = {Self-consistent sharp interface theory of active condensate dynamics},
author = {Andriy Goychuk and Leonardo Demarchi and Ivan Maryshev and Erwin Frey},
doi = {10.1103/PhysRevResearch.6.033082},
issn = {2643-1564},
year = {2024},
date = {2024-07-01},
urldate = {2024-07-01},
journal = {Physical Review Research},
volume = {6},
number = {3},
pages = {033082},
abstract = {Biomolecular condensates help organize the cell cytoplasm and nucleoplasm into spatial compartments with different chemical compositions. A key feature of such compositional patterning is the local enrichment of enzymatically active biomolecules which, after transient binding via molecular interactions, catalyze reactions among their substrates. Thereby, biomolecular condensates provide a spatial template for nonuniform concentration profiles of substrates. In turn, the concentration profiles of substrates, and their molecular interactions with enzymes, drive enzyme fluxes which can enable novel nonequilibrium dynamics. To analyze this generic class of systems, with a current focus on self-propelled droplet motion, we here develop a self-consistent sharp interface theory. In our theory, we diverge from the usual bottom-up approach, which involves calculating the dynamics of concentration profiles based on a given chemical potential gradient. Instead, reminiscent of control theory, we take the reverse approach by deriving the chemical potential profile and enzyme fluxes required to maintain a desired condensate form and dynamics. The chemical potential profile and currents of enzymes come with a corresponding power dissipation rate, which allows us to derive a thermodynamic consistency criterion for the passive part of the system (here, reciprocal enzyme-enzyme interactions). As a first-use case of our theory, we study the role of reciprocal interactions, where the transport of substrates due to reactions and diffusion is, in part, compensated by redistribution due to molecular interactions. More generally, our theory applies to mass-conserved active matter systems with moving phase boundaries.},
keywords = {Biomolecular Dynamics, Enzymes, Liquid-Liquid Phase Transition, Nonequilibrium Systems, Pattern Formation, Protein-Protein Interactions, Traveling Waves},
pubstate = {published},
tppubtype = {article}
}
Biomolecular condensates help organize the cell cytoplasm and nucleoplasm into spatial compartments with different chemical compositions. A key feature of such compositional patterning is the local enrichment of enzymatically active biomolecules which, after transient binding via molecular interactions, catalyze reactions among their substrates. Thereby, biomolecular condensates provide a spatial template for nonuniform concentration profiles of substrates. In turn, the concentration profiles of substrates, and their molecular interactions with enzymes, drive enzyme fluxes which can enable novel nonequilibrium dynamics. To analyze this generic class of systems, with a current focus on self-propelled droplet motion, we here develop a self-consistent sharp interface theory. In our theory, we diverge from the usual bottom-up approach, which involves calculating the dynamics of concentration profiles based on a given chemical potential gradient. Instead, reminiscent of control theory, we take the reverse approach by deriving the chemical potential profile and enzyme fluxes required to maintain a desired condensate form and dynamics. The chemical potential profile and currents of enzymes come with a corresponding power dissipation rate, which allows us to derive a thermodynamic consistency criterion for the passive part of the system (here, reciprocal enzyme-enzyme interactions). As a first-use case of our theory, we study the role of reciprocal interactions, where the transport of substrates due to reactions and diffusion is, in part, compensated by redistribution due to molecular interactions. More generally, our theory applies to mass-conserved active matter systems with moving phase boundaries.
2023
1
Enzyme-Enriched Condensates Show Self-Propulsion, Positioning, and Coexistence Open access
Leonardo Demarchi*; Andriy Goychuk†*; Ivan Maryshev; Erwin Frey†
* Equal contribution † Corresponding author
In: Physical Review Letters, vol. 130, no. 12, pp. 128401, 2023, ISSN: 0031-9007, 1079-7114.
Repository Abstract Links BibTeX
Analytical TheoryBiomolecular DynamicsEnzymesLiquid-Liquid Phase TransitionNonequilibrium SystemsPattern FormationProtein-Protein InteractionsSimulationTraveling Waves
In the press
@article{demarchi_enzyme-enriched_2023,
title = {Enzyme-Enriched Condensates Show Self-Propulsion, Positioning, and Coexistence},
author = {Leonardo Demarchi and Andriy Goychuk and Ivan Maryshev and Erwin Frey},
doi = {10.1103/PhysRevLett.130.128401},
issn = {0031-9007, 1079-7114},
year = {2023},
date = {2023-03-01},
urldate = {2023-03-01},
journal = {Physical Review Letters},
volume = {130},
number = {12},
pages = {128401},
abstract = {Enzyme-enriched condensates can organize the spatial distribution of their substrates by catalyzing nonequilibrium reactions. Conversely, an inhomogeneous substrate distribution induces enzyme fluxes through substrate-enzyme interactions. We find that condensates move toward the center of a confining domain when this feedback is weak. Above a feedback threshold, they exhibit self-propulsion, leading to oscillatory dynamics. Moreover, catalysis-driven enzyme fluxes can lead to interrupted coarsening, resulting in equidistant condensate positioning, and to condensate division.},
keywords = {Analytical Theory, Biomolecular Dynamics, Enzymes, Liquid-Liquid Phase Transition, Nonequilibrium Systems, Pattern Formation, Protein-Protein Interactions, Simulation, Traveling Waves},
pubstate = {published},
tppubtype = {article}
}
Enzyme-enriched condensates can organize the spatial distribution of their substrates by catalyzing nonequilibrium reactions. Conversely, an inhomogeneous substrate distribution induces enzyme fluxes through substrate-enzyme interactions. We find that condensates move toward the center of a confining domain when this feedback is weak. Above a feedback threshold, they exhibit self-propulsion, leading to oscillatory dynamics. Moreover, catalysis-driven enzyme fluxes can lead to interrupted coarsening, resulting in equidistant condensate positioning, and to condensate division.