2023
5.
Andriy Goychuk; Deepti Kannan; Arup K. Chakraborty; Mehran Kardar
Polymer folding through active processes recreates features of genome organization Journal Article
In: Proceedings of the National Academy of Sciences, vol. 120, no. 20, pp. e2221726120, 2023, ISSN: 0027-8424, 1091-6490.
Abstract | Links | BibTeX | Tags: Active Processes, Analytical Theory, Genome Organization, Polymer Mechanics, Simulation, Stochastic Processes
@article{goychuk_polymer_2023,
title = {Polymer folding through active processes recreates features of genome organization},
author = {Andriy Goychuk and Deepti Kannan and Arup K. Chakraborty and Mehran Kardar},
url = {https://pnas.org/doi/10.1073/pnas.2221726120},
doi = {10.1073/pnas.2221726120},
issn = {0027-8424, 1091-6490},
year = {2023},
date = {2023-05-01},
urldate = {2026-05-29},
journal = {Proceedings of the National Academy of Sciences},
volume = {120},
number = {20},
pages = {e2221726120},
abstract = {From proteins to chromosomes, polymers fold into specific conformations that control their biological function. Polymer folding has long been studied with equilibrium thermodynamics, yet intracellular organization and regulation involve energy-consuming, active processes. Signatures of activity have been measured in the context of chromatin motion, which shows spatial correlations and enhanced subdiffusion only in the presence of adenosine triphosphate. Moreover, chromatin motion varies with genomic coordinate, pointing toward a heterogeneous pattern of active processes along the sequence. How do such patterns of activity affect the conformation of a polymer such as chromatin? We address this question by combining analytical theory and simulations to study a polymer subjected to sequence-dependent correlated active forces. Our analysis shows that a local increase in activity (larger active forces) can cause the polymer backbone to bend and expand, while less active segments straighten out and condense. Our simulations further predict that modest activity differences can drive compartmentalization of the polymer consistent with the patterns observed in chromosome conformation capture experiments. Moreover, segments of the polymer that show correlated active (sub)diffusion attract each other through effective long-ranged harmonic interactions, whereas anticorrelations lead to effective repulsions. Thus, our theory offers nonequilibrium mechanisms for forming genomic compartments, which cannot be distinguished from affinity-based folding using structural data alone. As a first step toward exploring whether active mechanisms contribute to shaping genome conformations, we discuss a data-driven approach.},
keywords = {Active Processes, Analytical Theory, Genome Organization, Polymer Mechanics, Simulation, Stochastic Processes},
pubstate = {published},
tppubtype = {article}
}
From proteins to chromosomes, polymers fold into specific conformations that control their biological function. Polymer folding has long been studied with equilibrium thermodynamics, yet intracellular organization and regulation involve energy-consuming, active processes. Signatures of activity have been measured in the context of chromatin motion, which shows spatial correlations and enhanced subdiffusion only in the presence of adenosine triphosphate. Moreover, chromatin motion varies with genomic coordinate, pointing toward a heterogeneous pattern of active processes along the sequence. How do such patterns of activity affect the conformation of a polymer such as chromatin? We address this question by combining analytical theory and simulations to study a polymer subjected to sequence-dependent correlated active forces. Our analysis shows that a local increase in activity (larger active forces) can cause the polymer backbone to bend and expand, while less active segments straighten out and condense. Our simulations further predict that modest activity differences can drive compartmentalization of the polymer consistent with the patterns observed in chromosome conformation capture experiments. Moreover, segments of the polymer that show correlated active (sub)diffusion attract each other through effective long-ranged harmonic interactions, whereas anticorrelations lead to effective repulsions. Thus, our theory offers nonequilibrium mechanisms for forming genomic compartments, which cannot be distinguished from affinity-based folding using structural data alone. As a first step toward exploring whether active mechanisms contribute to shaping genome conformations, we discuss a data-driven approach.
4.
Leonardo Demarchi; Andriy Goychuk; Ivan Maryshev; Erwin Frey
Enzyme-Enriched Condensates Show Self-Propulsion, Positioning, and Coexistence Journal Article
In: Physical Review Letters, vol. 130, no. 12, pp. 128401, 2023, ISSN: 0031-9007, 1079-7114.
Abstract | Links | BibTeX | Tags: Analytical Theory, Biomolecular Dynamics, Enzymes, Liquid-Liquid Phase Transition, Nonequilibrium Systems, Pattern Formation, Protein-Protein Interactions, Simulation, Traveling Waves
@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},
url = {https://link.aps.org/doi/10.1103/PhysRevLett.130.128401},
doi = {10.1103/PhysRevLett.130.128401},
issn = {0031-9007, 1079-7114},
year = {2023},
date = {2023-03-01},
urldate = {2026-05-29},
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.
2021
3.
Pablo A. Fernández; Benedikt Buchmann; Andriy Goychuk; Lisa K. Engelbrecht; Marion K. Raich; Christina H. Scheel; Erwin Frey; Andreas R. Bausch
Surface-tension-induced budding drives alveologenesis in human mammary gland organoids Journal Article
In: Nature Physics, vol. 17, no. 10, pp. 1130–1136, 2021, ISSN: 1745-2473, 1745-2481.
Abstract | Links | BibTeX | Tags: Analytical Theory, Budding, Cell Migration, Collective Dynamics, Morphogenesis, Organoids, Shape Instability
@article{fernandez_surface-tension-induced_2021,
title = {Surface-tension-induced budding drives alveologenesis in human mammary gland organoids},
author = {Pablo A. Fernández and Benedikt Buchmann and Andriy Goychuk and Lisa K. Engelbrecht and Marion K. Raich and Christina H. Scheel and Erwin Frey and Andreas R. Bausch},
url = {https://www.nature.com/articles/s41567-021-01336-7},
doi = {10.1038/s41567-021-01336-7},
issn = {1745-2473, 1745-2481},
year = {2021},
date = {2021-10-01},
urldate = {2026-05-29},
journal = {Nature Physics},
volume = {17},
number = {10},
pages = {1130–1136},
abstract = {Organ development involves complex shape transformations driven by active mechanical stresses that sculpt the growing tissue1,2. Epithelial gland morphogenesis is a prominent example where cylindrical branches transform into spherical alveoli during growth3,4,5. Here we show that this shape transformation is induced by a local change from anisotropic to isotropic tension within the epithelial cell layer of developing human mammary gland organoids. By combining laser ablation with optical force inference and theoretical analysis, we demonstrate that circumferential tension increases at the expense of axial tension through a reorientation of cells that correlates with the onset of persistent collective rotation around the branch axis. This enables the tissue to locally control the onset of a generalized Rayleigh–Plateau instability, leading to spherical tissue buds6. The interplay between cell motion, cell orientation and tissue tension is a generic principle that may turn out to drive shape transformations in other cell tissues.},
keywords = {Analytical Theory, Budding, Cell Migration, Collective Dynamics, Morphogenesis, Organoids, Shape Instability},
pubstate = {published},
tppubtype = {article}
}
Organ development involves complex shape transformations driven by active mechanical stresses that sculpt the growing tissue1,2. Epithelial gland morphogenesis is a prominent example where cylindrical branches transform into spherical alveoli during growth3,4,5. Here we show that this shape transformation is induced by a local change from anisotropic to isotropic tension within the epithelial cell layer of developing human mammary gland organoids. By combining laser ablation with optical force inference and theoretical analysis, we demonstrate that circumferential tension increases at the expense of axial tension through a reorientation of cells that correlates with the onset of persistent collective rotation around the branch axis. This enables the tissue to locally control the onset of a generalized Rayleigh–Plateau instability, leading to spherical tissue buds6. The interplay between cell motion, cell orientation and tissue tension is a generic principle that may turn out to drive shape transformations in other cell tissues.
2.
Beatrice Ramm; Andriy Goychuk; Alena Khmelinskaia; Philipp Blumhardt; Hiromune Eto; Kristina A. Ganzinger; Erwin Frey; Petra Schwille
A diffusiophoretic mechanism for ATP-driven transport without motor proteins Journal Article
In: Nature Physics, vol. 17, no. 7, pp. 850–858, 2021, ISSN: 1745-2473, 1745-2481.
Abstract | Links | BibTeX | Tags: Analytical Theory, Diffusiophoresis, Nonequilibrium Dynamics, Pattern Formation, Transport
@article{ramm_diffusiophoretic_2021,
title = {A diffusiophoretic mechanism for ATP-driven transport without motor proteins},
author = {Beatrice Ramm and Andriy Goychuk and Alena Khmelinskaia and Philipp Blumhardt and Hiromune Eto and Kristina A. Ganzinger and Erwin Frey and Petra Schwille},
url = {https://www.nature.com/articles/s41567-021-01213-3},
doi = {10.1038/s41567-021-01213-3},
issn = {1745-2473, 1745-2481},
year = {2021},
date = {2021-07-01},
urldate = {2026-05-29},
journal = {Nature Physics},
volume = {17},
number = {7},
pages = {850–858},
abstract = {The healthy growth and maintenance of a biological system depends on the precise spatial organization of molecules within the cell through the dissipation of energy. Reaction–diffusion mechanisms can facilitate this organization, as can directional cargo transport orchestrated by motor proteins, by relying on specific protein interactions. However, transport of material through the cell can also be achieved by active processes based on non-specific, purely physical mechanisms, a phenomenon that remains poorly explored. Here, using a combined experimental and theoretical approach, we discover and describe a hidden function of the Escherichia coli MinDE protein system: in addition to forming dynamic patterns, this system accomplishes the directional active transport of functionally unrelated cargo on membranes. Remarkably, this mechanism enables the sorting of diffusive objects according to their effective size, as evidenced using modular DNA origami–streptavidin nanostructures. We show that the diffusive fluxes of MinDE and non-specific cargo couple via density-dependent friction. This non-specific process constitutes a diffusiophoretic mechanism, as yet unknown in a cell biology setting. This nonlinear coupling between diffusive fluxes could represent a generic physical mechanism for establishing intracellular organization.},
keywords = {Analytical Theory, Diffusiophoresis, Nonequilibrium Dynamics, Pattern Formation, Transport},
pubstate = {published},
tppubtype = {article}
}
The healthy growth and maintenance of a biological system depends on the precise spatial organization of molecules within the cell through the dissipation of energy. Reaction–diffusion mechanisms can facilitate this organization, as can directional cargo transport orchestrated by motor proteins, by relying on specific protein interactions. However, transport of material through the cell can also be achieved by active processes based on non-specific, purely physical mechanisms, a phenomenon that remains poorly explored. Here, using a combined experimental and theoretical approach, we discover and describe a hidden function of the Escherichia coli MinDE protein system: in addition to forming dynamic patterns, this system accomplishes the directional active transport of functionally unrelated cargo on membranes. Remarkably, this mechanism enables the sorting of diffusive objects according to their effective size, as evidenced using modular DNA origami–streptavidin nanostructures. We show that the diffusive fluxes of MinDE and non-specific cargo couple via density-dependent friction. This non-specific process constitutes a diffusiophoretic mechanism, as yet unknown in a cell biology setting. This nonlinear coupling between diffusive fluxes could represent a generic physical mechanism for establishing intracellular organization.
2019
1.
Andriy Goychuk; Erwin Frey
Protein Recruitment through Indirect Mechanochemical Interactions Journal Article
In: Physical Review Letters, vol. 123, no. 17, pp. 178101, 2019, ISSN: 0031-9007, 1079-7114.
Abstract | Links | BibTeX | Tags: Analytical Theory, Biomolecular Self-Assembly, Elastic Deformation, First Passage Problems, Mean Field Theory, Pattern Formation, Protein-Membrane Interactions, Protein-Protein Interactions
@article{goychuk_protein_2019,
title = {Protein Recruitment through Indirect Mechanochemical Interactions},
author = {Andriy Goychuk and Erwin Frey},
url = {https://link.aps.org/doi/10.1103/PhysRevLett.123.178101},
doi = {10.1103/PhysRevLett.123.178101},
issn = {0031-9007, 1079-7114},
year = {2019},
date = {2019-10-01},
urldate = {2026-05-29},
journal = {Physical Review Letters},
volume = {123},
number = {17},
pages = {178101},
abstract = {Some of the key proteins essential for important cellular processes are capable of recruiting other proteins from the cytosol to phospholipid membranes. The physical basis for this cooperativity of binding is, surprisingly, still unclear. Here, we suggest a general feedback mechanism that explains cooperativity through mechanochemical coupling mediated by the mechanical properties of phospholipid membranes. Our theory predicts that protein recruitment, and therefore also protein pattern formation, involves membrane deformation and is strongly affected by membrane composition.},
keywords = {Analytical Theory, Biomolecular Self-Assembly, Elastic Deformation, First Passage Problems, Mean Field Theory, Pattern Formation, Protein-Membrane Interactions, Protein-Protein Interactions},
pubstate = {published},
tppubtype = {article}
}
Some of the key proteins essential for important cellular processes are capable of recruiting other proteins from the cytosol to phospholipid membranes. The physical basis for this cooperativity of binding is, surprisingly, still unclear. Here, we suggest a general feedback mechanism that explains cooperativity through mechanochemical coupling mediated by the mechanical properties of phospholipid membranes. Our theory predicts that protein recruitment, and therefore also protein pattern formation, involves membrane deformation and is strongly affected by membrane composition.