2026
23
Hidden nonreciprocity as a stabilizing effective potential in active matter Open access
Matthew Du; Andriy Goychuk; Suriyanarayanan Vaikuntanathan
In: Physical Review Research, vol. 8, no. 3, pp. 033330, 2026, ISSN: 2643-1564.
@article{du_hidden_2026,
title = {Hidden nonreciprocity as a stabilizing effective potential in active matter},
author = {Matthew Du and Andriy Goychuk and Suriyanarayanan Vaikuntanathan},
doi = {10.1103/23zn-lzx2},
issn = {2643-1564},
year = {2026},
date = {2026-09-01},
urldate = {2026-09-01},
journal = {Physical Review Research},
volume = {8},
number = {3},
pages = {033330},
abstract = {Nonreciprocal interactions are known to produce distinctive dynamics in active matter. To shed light on how the stationary state of such systems is affected by breaking reciprocity, we consider interacting particles propelled by persistent noise, where reciprocity is broken by a transverse force perpendicular to the gradient of the interaction energy. Focusing on the steady-state distribution of positions, we show that the nonreciprocal coupling helps keep the system at its stable configurations. Specifically, we demonstrate this effect for a variety of active systems whose stable configurations are energy minima, finding that the nonreciprocal coupling stiffens springs, aligns spins, and improves associative memory. In contrast, the transverse force does not change the stationary distribution of positions at all when the noise is thermal. Preliminary simulations suggest that this nonreciprocal coupling plays a similar stabilizing role in other active systems, such as those exhibiting motility-induced phase separation, whose stable configurations are not energy minima.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Nonreciprocal interactions are known to produce distinctive dynamics in active matter. To shed light on how the stationary state of such systems is affected by breaking reciprocity, we consider interacting particles propelled by persistent noise, where reciprocity is broken by a transverse force perpendicular to the gradient of the interaction energy. Focusing on the steady-state distribution of positions, we show that the nonreciprocal coupling helps keep the system at its stable configurations. Specifically, we demonstrate this effect for a variety of active systems whose stable configurations are energy minima, finding that the nonreciprocal coupling stiffens springs, aligns spins, and improves associative memory. In contrast, the transverse force does not change the stationary distribution of positions at all when the noise is thermal. Preliminary simulations suggest that this nonreciprocal coupling plays a similar stabilizing role in other active systems, such as those exhibiting motility-induced phase separation, whose stable configurations are not energy minima.
22
Biophysical properties of IgD determine thresholds for self-tolerance and selection into germinal centers Preprint
Lachlan P. Deimel; Ryan A. Brady; Andriy Goychuk; Gabriela S Silva Santos; Clara Uhe; Andrew J. MacLean; Brianna Hernandez; Shuai Zong; Laurine Binet; Mary Tenuta; Dennis Shaefer-Babajew; Zeliha Kilic; Anna Gazumyan; Thiago Y. Oliveira; Harald Hartweger; Arup K. Chakraborty; Scott C. Blanchard; Michel C. Nussenzweig
bioRxiv, 2026.
@preprint{deimel_biophysical_2026,
title = {Biophysical properties of IgD determine thresholds for self-tolerance and selection into germinal centers},
author = {Lachlan P. Deimel and Ryan A. Brady and Andriy Goychuk and Gabriela S Silva Santos and Clara Uhe and Andrew J. MacLean and Brianna Hernandez and Shuai Zong and Laurine Binet and Mary Tenuta and Dennis Shaefer-Babajew and Zeliha Kilic and Anna Gazumyan and Thiago Y. Oliveira and Harald Hartweger and Arup K. Chakraborty and Scott C. Blanchard and Michel C. Nussenzweig},
url = {http://biorxiv.org/lookup/doi/10.64898/2026.07.02.735902},
doi = {10.64898/2026.07.02.735902},
year = {2026},
date = {2026-07-01},
urldate = {2026-07-01},
publisher = {Immunology},
abstract = {Summary
Immunoglobulin D (IgD) is among the most conserved antibody isotypes, found in virtually all jawed vertebrates
1
. Unlike other isotypes, IgD contains an unusually long hinge region of up to 160 amino acids that connects the constant and variable regions. Its expression pattern is also conserved; IgD is co-expressed with IgM on transitional and mature naïve B cells. However, the function of IgD has remained enigmatic since its discovery in 1965
2,3
. Here we present and test a biophysical model positing that IgD increases the entropic cost of bivalent antigen binding. Single-molecule measurements revealed that the antigen-binding arms of IgD are substantially more dynamic than those of IgM, suggesting that cell surface IgD would be energetically penalized in bivalent antigen binding. Consistent with the model and biophysical data, we find that the long hinge compromises antigen capture by IgD B cell receptors (BCRs) compared to IgM BCRs. To determine how the difference in antigen binding impacts immunity, we produced mice that express only IgM and IgD, exclusively IgM or IgD, or IgD with a truncated hinge region. The data indicate that the increased entropic cost of antigen binding imposed by the IgD hinge attenuates negative selection by self-antigen while increasing the affinity-based threshold for positive selection into the germinal center (GC). Together the results indicate that IgD functions physiologically to desensitize B cells to antigen, thereby expanding the B cell repertoire while optimizing affinity-based selection into the GC.},
howpublished = {bioRxiv},
keywords = {},
pubstate = {published},
tppubtype = {preprint}
}
Summary
Immunoglobulin D (IgD) is among the most conserved antibody isotypes, found in virtually all jawed vertebrates
1
. Unlike other isotypes, IgD contains an unusually long hinge region of up to 160 amino acids that connects the constant and variable regions. Its expression pattern is also conserved; IgD is co-expressed with IgM on transitional and mature naïve B cells. However, the function of IgD has remained enigmatic since its discovery in 1965
2,3
. Here we present and test a biophysical model positing that IgD increases the entropic cost of bivalent antigen binding. Single-molecule measurements revealed that the antigen-binding arms of IgD are substantially more dynamic than those of IgM, suggesting that cell surface IgD would be energetically penalized in bivalent antigen binding. Consistent with the model and biophysical data, we find that the long hinge compromises antigen capture by IgD B cell receptors (BCRs) compared to IgM BCRs. To determine how the difference in antigen binding impacts immunity, we produced mice that express only IgM and IgD, exclusively IgM or IgD, or IgD with a truncated hinge region. The data indicate that the increased entropic cost of antigen binding imposed by the IgD hinge attenuates negative selection by self-antigen while increasing the affinity-based threshold for positive selection into the germinal center (GC). Together the results indicate that IgD functions physiologically to desensitize B cells to antigen, thereby expanding the B cell repertoire while optimizing affinity-based selection into the GC.
Immunoglobulin D (IgD) is among the most conserved antibody isotypes, found in virtually all jawed vertebrates
1
. Unlike other isotypes, IgD contains an unusually long hinge region of up to 160 amino acids that connects the constant and variable regions. Its expression pattern is also conserved; IgD is co-expressed with IgM on transitional and mature naïve B cells. However, the function of IgD has remained enigmatic since its discovery in 1965
2,3
. Here we present and test a biophysical model positing that IgD increases the entropic cost of bivalent antigen binding. Single-molecule measurements revealed that the antigen-binding arms of IgD are substantially more dynamic than those of IgM, suggesting that cell surface IgD would be energetically penalized in bivalent antigen binding. Consistent with the model and biophysical data, we find that the long hinge compromises antigen capture by IgD B cell receptors (BCRs) compared to IgM BCRs. To determine how the difference in antigen binding impacts immunity, we produced mice that express only IgM and IgD, exclusively IgM or IgD, or IgD with a truncated hinge region. The data indicate that the increased entropic cost of antigen binding imposed by the IgD hinge attenuates negative selection by self-antigen while increasing the affinity-based threshold for positive selection into the germinal center (GC). Together the results indicate that IgD functions physiologically to desensitize B cells to antigen, thereby expanding the B cell repertoire while optimizing affinity-based selection into the GC.
21
Externally driven condensates show translation-induced polarization, directed coalescence, and anomalous diffusion in viscoelastic media Open access
In: Physical Review E, vol. 113, iss. 6, no. 6, pp. 065402, 2026, ISSN: 2470-0045, 2470-0053.
Repository Abstract Links BibTeX
@article{andriy_goychuk_externally_2026,
title = {Externally driven condensates show translation-induced polarization, directed coalescence, and anomalous diffusion in viscoelastic media},
author = {Andriy Goychuk},
doi = {10.1103/n662-39rs},
issn = {2470-0045, 2470-0053},
year = {2026},
date = {2026-05-01},
urldate = {2026-05-01},
journal = {Physical Review E},
volume = {113},
number = {6},
issue = {6},
pages = {065402},
abstract = {Phase separation into compositionally and physically distinct domains is ubiquitous in (non)living matter ranging from alloys and emulsions to biomolecular condensates in cells. The organization of these domains can be controlled, for example, by nonequilibrium chemical reactions, external fields, or mechanical stresses. In this context, stationary states can emerge from effective long-range interactions resembling the electrostatics of charges. As shown here, externally controlled dynamic states, such as condensate motion, lead to an effective polarization and dipolar force fields even for microscopically nonpolarizable matter. The dipole-dipole interactions resulting from this translation-induced polarization cause directed coalescence of domains. This coarsening mechanism complements Ostwald ripening and coalescence due to Brownian motion or Marangoni flows, and has implications for controlling domains by electric fields or concentration gradients. Interestingly, the chemical potential gradients around a domain that nucleates material are exactly opposite to the hydrodynamic pressure gradients around an impermeable colloid that pushes the fluid, suggesting a competition between phase separation and hydrodynamics. In addition to chemical control, the motion of domains can also be driven by mechanical stresses. An example is the cell interior, where mechanical stresses are actively generated by molecular motors and opposed by passive viscoelastic stresses in the cytoplasm and nucleoplasm. The resulting fluid flows lead to Brownian motion with a suppressed or enhanced size scaling which modifies collision-coalescence. For active stresses with a long correlation time, the domains show superdiffusion on intermediate time scales. Together, these findings shed new light on the dynamics of domains in viscoelastic media and conserved order parameters in general.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Phase separation into compositionally and physically distinct domains is ubiquitous in (non)living matter ranging from alloys and emulsions to biomolecular condensates in cells. The organization of these domains can be controlled, for example, by nonequilibrium chemical reactions, external fields, or mechanical stresses. In this context, stationary states can emerge from effective long-range interactions resembling the electrostatics of charges. As shown here, externally controlled dynamic states, such as condensate motion, lead to an effective polarization and dipolar force fields even for microscopically nonpolarizable matter. The dipole-dipole interactions resulting from this translation-induced polarization cause directed coalescence of domains. This coarsening mechanism complements Ostwald ripening and coalescence due to Brownian motion or Marangoni flows, and has implications for controlling domains by electric fields or concentration gradients. Interestingly, the chemical potential gradients around a domain that nucleates material are exactly opposite to the hydrodynamic pressure gradients around an impermeable colloid that pushes the fluid, suggesting a competition between phase separation and hydrodynamics. In addition to chemical control, the motion of domains can also be driven by mechanical stresses. An example is the cell interior, where mechanical stresses are actively generated by molecular motors and opposed by passive viscoelastic stresses in the cytoplasm and nucleoplasm. The resulting fluid flows lead to Brownian motion with a suppressed or enhanced size scaling which modifies collision-coalescence. For active stresses with a long correlation time, the domains show superdiffusion on intermediate time scales. Together, these findings shed new light on the dynamics of domains in viscoelastic media and conserved order parameters in general.
20
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.
19
Interplay between the immune response and the adaptation of metabolic pathways upon infection Preprint
Andriy Goychuk; David Goh; Sergio Eraso; Ruslan Medzhitov; Arup K. Chakraborty
bioRxiv, 2026.
Glucose RegulationImmunologyInflammationMetabolism
@preprint{goychuk_interplay_2026,
title = {Interplay between the immune response and the adaptation of metabolic pathways upon infection},
author = {Andriy Goychuk and David Goh and Sergio Eraso and Ruslan Medzhitov and Arup K. Chakraborty},
doi = {10.64898/2026.01.02.697260},
year = {2026},
date = {2026-01-01},
urldate = {2026-01-01},
publisher = {Immunology},
abstract = {Glucose is the principal metabolic fuel for the energy needs of most cell types. Upon infection, cytokines secreted by the immune system regulate redistribution of glucose to meet new metabolic needs associated with clearing the pathogen. We develop a mathematical model to describe the dynamics of such adaptation of metabolic pathways mediated by the immune response and its impact on the ability to clear pathogen and restore health. We find that cytokine-regulated redistribution of glucose resources in different tissues is critical for an effective immune response to pathogen as strictly clamping plasma glucose levels to homeostatic levels results in an ineffective immune response. By studying the effects of various parameters in our model, we describe how aberrant regulation of adaptation mechanisms affect outcomes of infection. Too high a glucose consumption rate by innate immune cells to mediate functions results in failure to clear pathogen. Pathogens with a very high replication rate can be controlled to low levels, but at a very high metabolic cost. Too low a pathogen replication rate allows the pathogen to hide from the immune system and rebound to high levels at later times. Finally, the strength of the innate immune response must be regulated to not be too high, not only to limit immunopathogenesis, but also for mediating an effective adaptive immune response.},
howpublished = {bioRxiv},
keywords = {Glucose Regulation, Immunology, Inflammation, Metabolism},
pubstate = {published},
tppubtype = {preprint}
}
Glucose is the principal metabolic fuel for the energy needs of most cell types. Upon infection, cytokines secreted by the immune system regulate redistribution of glucose to meet new metabolic needs associated with clearing the pathogen. We develop a mathematical model to describe the dynamics of such adaptation of metabolic pathways mediated by the immune response and its impact on the ability to clear pathogen and restore health. We find that cytokine-regulated redistribution of glucose resources in different tissues is critical for an effective immune response to pathogen as strictly clamping plasma glucose levels to homeostatic levels results in an ineffective immune response. By studying the effects of various parameters in our model, we describe how aberrant regulation of adaptation mechanisms affect outcomes of infection. Too high a glucose consumption rate by innate immune cells to mediate functions results in failure to clear pathogen. Pathogens with a very high replication rate can be controlled to low levels, but at a very high metabolic cost. Too low a pathogen replication rate allows the pathogen to hide from the immune system and rebound to high levels at later times. Finally, the strength of the innate immune response must be regulated to not be too high, not only to limit immunopathogenesis, but also for mediating an effective adaptive immune response.
18
Active fluctuations induce buckling of living surfaces Preprint
Matteo Ciarchi; Andriy Goychuk; Erwin Frey
arXiv, 2026.
Active MatterSoft Condensed MatterStatistical Mechanics
@preprint{ciarchi_active_2026,
title = {Active fluctuations induce buckling of living surfaces},
author = {Matteo Ciarchi and Andriy Goychuk and Erwin Frey},
doi = {10.48550/ARXIV.2602.24272},
year = {2026},
date = {2026-01-01},
urldate = {2026-01-01},
publisher = {arXiv},
abstract = {Active tissues exhibit tension fluctuations that are correlated in space and time. We study a minimal overdamped surface model in which such fluctuations enter as a zero-mean, multiplicative modulation of the local surface tension. Although the deterministic elastic dynamics (tension plus bending) stabilizes the flat state for all nonzero wave numbers, we find that sufficiently persistent active fluctuations generate positive ensemble growth rates for a finite band of Fourier modes, leading to stochastic buckling with wavelength selection. A non-Markovian theory based on the Novikov–Furutsu theorem captures the instability threshold and unstable band observed in simulations.},
howpublished = {arXiv},
keywords = {Active Matter, Soft Condensed Matter, Statistical Mechanics},
pubstate = {published},
tppubtype = {preprint}
}
Active tissues exhibit tension fluctuations that are correlated in space and time. We study a minimal overdamped surface model in which such fluctuations enter as a zero-mean, multiplicative modulation of the local surface tension. Although the deterministic elastic dynamics (tension plus bending) stabilizes the flat state for all nonzero wave numbers, we find that sufficiently persistent active fluctuations generate positive ensemble growth rates for a finite band of Fourier modes, leading to stochastic buckling with wavelength selection. A non-Markovian theory based on the Novikov–Furutsu theorem captures the instability threshold and unstable band observed in simulations.
17
Dynamical mean-field theory of active, self-interacting heteropolymers Preprint
2026.
Repository Abstract Links BibTeX
Mean Field TheoryPolymersSoft Condensed Matter
@preprint{goychuk_gaussian_2026,
title = {Dynamical mean-field theory of active, self-interacting heteropolymers},
author = {Andriy Goychuk},
doi = {10.48550/ARXIV.2604.02085},
year = {2026},
date = {2026-01-01},
urldate = {2026-01-01},
publisher = {arXiv},
abstract = {Analytical theories of polymer dynamics typically focus on the linear response around some steady state obtained via perturbative calculations. The present study derives a dynamical, nonlinear mean-field theory that yields unified access to the evolution of conformations, contact probabilities, and fluctuations of active polymers within a single analytical framework. As in previous mean-field descriptions of passive polymers, the object of interest is the two-point correlator, which is the lowest-order relevant observable in the general Langevin equation of a polymer. In contrast, the present focus is on active polymers driven by heterogeneous monomer-level kicks and spatially correlated active flows, while allowing nonreciprocal couplings, in the presence of hydrodynamic and contact interactions. Using a Gaussian closure to truncate higher-order correlations leads to a self-consistent diffusion equation for the chain correlations. In some cases, this can be further simplified to the dynamics of pairwise squared separations in closed form. In the continuum limit, the theory reveals useful analogies to similar mean-field approximations for reaction-diffusion systems, as well as fractional diffusion in different scale-free regimes. Deriving asymptotic solutions in different parameter regimes of the continuum limit recovers the scalings of coiled, globular, and self-avoiding polymers, thus validating the theory. Applied to hydrodynamically coupled active polymers, such as chromatin, the framework predicts a sequence of crossover scalings between coiled, swollen, and hyper-compacted fractal states.},
keywords = {Mean Field Theory, Polymers, Soft Condensed Matter},
pubstate = {published},
tppubtype = {preprint}
}
Analytical theories of polymer dynamics typically focus on the linear response around some steady state obtained via perturbative calculations. The present study derives a dynamical, nonlinear mean-field theory that yields unified access to the evolution of conformations, contact probabilities, and fluctuations of active polymers within a single analytical framework. As in previous mean-field descriptions of passive polymers, the object of interest is the two-point correlator, which is the lowest-order relevant observable in the general Langevin equation of a polymer. In contrast, the present focus is on active polymers driven by heterogeneous monomer-level kicks and spatially correlated active flows, while allowing nonreciprocal couplings, in the presence of hydrodynamic and contact interactions. Using a Gaussian closure to truncate higher-order correlations leads to a self-consistent diffusion equation for the chain correlations. In some cases, this can be further simplified to the dynamics of pairwise squared separations in closed form. In the continuum limit, the theory reveals useful analogies to similar mean-field approximations for reaction-diffusion systems, as well as fractional diffusion in different scale-free regimes. Deriving asymptotic solutions in different parameter regimes of the continuum limit recovers the scalings of coiled, globular, and self-avoiding polymers, thus validating the theory. Applied to hydrodynamically coupled active polymers, such as chromatin, the framework predicts a sequence of crossover scalings between coiled, swollen, and hyper-compacted fractal states.
2025
16
RNA gradients can guide condensates toward promoters: Implications for enhancer–promoter contacts and condensate-promoter kissing Open access
David Goh*; Deepti Kannan*; Pradeep Natarajan*; Andriy Goychuk†; Arup K. Chakraborty†
* Equal contribution † Corresponding author
In: The Journal of Chemical Physics, vol. 163, iss. 10, pp. 104905, 2025, ISSN: 0021-9606, 1089-7690.
Repository Abstract Links BibTeX
Biological PhysicsBiomolecular InteractionsChromatinGene transcriptionPhase transitionsPolymersProtein-Protein-InteractionsReentrantRibonucleic AcidSimulation
@article{goh_rna_2025,
title = {RNA gradients can guide condensates toward promoters: Implications for enhancer–promoter contacts and condensate-promoter kissing},
author = {David Goh and Deepti Kannan and Pradeep Natarajan and Andriy Goychuk and Arup K. Chakraborty},
doi = {10.1063/5.0277838},
issn = {0021-9606, 1089-7690},
year = {2025},
date = {2025-09-01},
urldate = {2025-09-01},
journal = {The Journal of Chemical Physics},
volume = {163},
issue = {10},
pages = {104905},
abstract = {We study how protein condensates respond to a site of active RNA transcription (i.e., a gene promoter) due to electrostatic protein–RNA interactions. Our results indicate that condensates can show directed motion toward the promoter, driven by gradients in the RNA concentration. Analytical theory, consistent with simulations, predicts that the droplet velocity has a non-monotonic dependence on the distance to the promoter. We explore the consequences of this gradient-sensing mechanism for enhancer–promoter (E–P) communication using polymer simulations of the intervening chromatin chain. Directed motion of enhancer-bound condensates can, together with loop extrusion by cohesin, collaboratively increase the enhancer–promoter contact probability. Finally, we investigate under which conditions condensates can exhibit oscillations in their morphology and in the distance to the promoter. Oscillatory dynamics are caused by a delayed response of transcription to condensate-promoter contact and negative feedback from the accumulation of RNA at the promoter, which results in charge repulsion.},
keywords = {Biological Physics, Biomolecular Interactions, Chromatin, Gene transcription, Phase transitions, Polymers, Protein-Protein-Interactions, Reentrant, Ribonucleic Acid, Simulation},
pubstate = {published},
tppubtype = {article}
}
We study how protein condensates respond to a site of active RNA transcription (i.e., a gene promoter) due to electrostatic protein–RNA interactions. Our results indicate that condensates can show directed motion toward the promoter, driven by gradients in the RNA concentration. Analytical theory, consistent with simulations, predicts that the droplet velocity has a non-monotonic dependence on the distance to the promoter. We explore the consequences of this gradient-sensing mechanism for enhancer–promoter (E–P) communication using polymer simulations of the intervening chromatin chain. Directed motion of enhancer-bound condensates can, together with loop extrusion by cohesin, collaboratively increase the enhancer–promoter contact probability. Finally, we investigate under which conditions condensates can exhibit oscillations in their morphology and in the distance to the promoter. Oscillatory dynamics are caused by a delayed response of transcription to condensate-promoter contact and negative feedback from the accumulation of RNA at the promoter, which results in charge repulsion.
2024
15
Delayed Excitations Induce Polymer Looping and Coherent Motion Open access
Andriy Goychuk†; Deepti Kannan; Mehran Kardar†
† Corresponding author
In: Physical Review Letters, vol. 133, iss. 7, pp. 078101, 2024, ISSN: 0031-9007, 1079-7114.
Preprint Repository Abstract Links BibTeX
ChromatinLangevin EquationLiving Matter & Active MatterPolymer BehaviorPolymersWormlike Chain Model
In the press
@article{goychuk_delayed_2024,
title = {Delayed Excitations Induce Polymer Looping and Coherent Motion},
author = {Andriy Goychuk and Deepti Kannan and Mehran Kardar},
doi = {10.1103/PhysRevLett.133.078101},
issn = {0031-9007, 1079-7114},
year = {2024},
date = {2024-08-01},
urldate = {2024-08-01},
journal = {Physical Review Letters},
volume = {133},
issue = {7},
pages = {078101},
abstract = {We consider inhomogeneous polymers driven by energy-consuming active processes which encode temporal patterns of athermal kicks. We find that such temporal excitation programs, propagated by tension along the polymer, can effectively couple distinct polymer loci. Consequently, distant loci exhibit correlated motions that fold the polymer into specific conformations, as set by the local actions of the active processes and their distribution along the polymer. Interestingly, active kicks that are canceled out by a time-delayed echo can induce strong compaction of the active polymer.},
keywords = {Chromatin, Langevin Equation, Living Matter & Active Matter, Polymer Behavior, Polymers, Wormlike Chain Model},
pubstate = {published},
tppubtype = {article}
}
We consider inhomogeneous polymers driven by energy-consuming active processes which encode temporal patterns of athermal kicks. We find that such temporal excitation programs, propagated by tension along the polymer, can effectively couple distinct polymer loci. Consequently, distant loci exhibit correlated motions that fold the polymer into specific conformations, as set by the local actions of the active processes and their distribution along the polymer. Interestingly, active kicks that are canceled out by a time-delayed echo can induce strong compaction of the active polymer.
14
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
13
Geometry-induced patterns through mechanochemical coupling Open access
Laeschkir Würthner*; Andriy Goychuk*; Erwin Frey
* Equal contribution
In: Physical Review E, vol. 108, no. 1, pp. 014404, 2023, ISSN: 2470-0045, 2470-0053.
Biological Self-OrganizationCell MembraneDifferential EquationsFinite-Element MethodPattern FormationPhase Space MethodsProtein Interaction NetworksProtein-Membrane Interactions
@article{wurthner_geometry-induced_2023,
title = {Geometry-induced patterns through mechanochemical coupling},
author = {Laeschkir Würthner and Andriy Goychuk and Erwin Frey},
doi = {10.1103/PhysRevE.108.014404},
issn = {2470-0045, 2470-0053},
year = {2023},
date = {2023-07-01},
urldate = {2023-07-01},
journal = {Physical Review E},
volume = {108},
number = {1},
pages = {014404},
abstract = {Intracellular protein patterns regulate a variety of vital cellular processes such as cell division and motility, which often involve dynamic cell-shape changes. These changes in cell shape may in turn affect the dynamics of pattern-forming proteins, hence leading to an intricate feedback loop between cell shape and chemical dynamics. While several computational studies have examined the rich resulting dynamics, the underlying mechanisms are not yet fully understood. To elucidate some of these mechanisms, we explore a conceptual model for cell polarity on a dynamic one-dimensional manifold. Using concepts from differential geometry, we derive the equations governing mass-conserving reaction–diffusion systems on time-evolving manifolds. Analyzing these equations mathematically, we show that dynamic shape changes of the membrane can induce pattern-forming instabilities in parts of the membrane, which we refer to as regional instabilities. Deformations of the local membrane geometry can also (regionally) suppress pattern formation and spatially shift already existing patterns. We explain our findings by applying and generalizing the local equilibria theory of mass-conserving reaction–diffusion systems. This allows us to determine a simple onset criterion for geometry-induced pattern-forming instabilities, which is linked to the phase-space structure of the reaction–diffusion system. The feedback loop between membrane shape deformations and reaction–diffusion dynamics then leads to a surprisingly rich phenomenology of patterns, including oscillations, traveling waves, and standing waves, even if these patterns do not occur in systems with a fixed membrane shape. Our paper reveals that the local conformation of the membrane geometry acts as an important dynamical control parameter for pattern formation in mass-conserving reaction-diffusion systems.},
keywords = {Biological Self-Organization, Cell Membrane, Differential Equations, Finite-Element Method, Pattern Formation, Phase Space Methods, Protein Interaction Networks, Protein-Membrane Interactions},
pubstate = {published},
tppubtype = {article}
}
Intracellular protein patterns regulate a variety of vital cellular processes such as cell division and motility, which often involve dynamic cell-shape changes. These changes in cell shape may in turn affect the dynamics of pattern-forming proteins, hence leading to an intricate feedback loop between cell shape and chemical dynamics. While several computational studies have examined the rich resulting dynamics, the underlying mechanisms are not yet fully understood. To elucidate some of these mechanisms, we explore a conceptual model for cell polarity on a dynamic one-dimensional manifold. Using concepts from differential geometry, we derive the equations governing mass-conserving reaction–diffusion systems on time-evolving manifolds. Analyzing these equations mathematically, we show that dynamic shape changes of the membrane can induce pattern-forming instabilities in parts of the membrane, which we refer to as regional instabilities. Deformations of the local membrane geometry can also (regionally) suppress pattern formation and spatially shift already existing patterns. We explain our findings by applying and generalizing the local equilibria theory of mass-conserving reaction–diffusion systems. This allows us to determine a simple onset criterion for geometry-induced pattern-forming instabilities, which is linked to the phase-space structure of the reaction–diffusion system. The feedback loop between membrane shape deformations and reaction–diffusion dynamics then leads to a surprisingly rich phenomenology of patterns, including oscillations, traveling waves, and standing waves, even if these patterns do not occur in systems with a fixed membrane shape. Our paper reveals that the local conformation of the membrane geometry acts as an important dynamical control parameter for pattern formation in mass-conserving reaction-diffusion systems.
12
Polymer folding through active processes recreates features of genome organization
Andriy Goychuk*; Deepti Kannan*; Arup K. Chakraborty†; Mehran Kardar†
* Equal contribution † Corresponding author
In: Proceedings of the National Academy of Sciences, vol. 120, no. 20, pp. e2221726120, 2023, ISSN: 0027-8424, 1091-6490.
Repository Abstract Links BibTeX
Active ProcessesAnalytical TheoryGenome OrganizationPolymer MechanicsSimulationStochastic 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},
doi = {10.1073/pnas.2221726120},
issn = {0027-8424, 1091-6490},
year = {2023},
date = {2023-05-01},
urldate = {2023-05-01},
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.
11
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.
2021
10
Optically transparent vertical silicon nanowire arrays for live-cell imaging
Roey Elnathan; Andrew W. Holle; Jennifer Young; Marina A. George; Omri Heifler; Andriy Goychuk; Erwin Frey; Ralf Kemkemer; Joachim P. Spatz; Alon Kosloff; Fernando Patolsky; Nicolas H. Voelcker
In: Journal of Nanobiotechnology, vol. 19, no. 1, pp. 51, 2021, ISSN: 1477-3155.
Biomaterials-CellsBionanoelectronicsIntracellular Delivery Techniques for Biomolecular ApplicationsNanofabrication and NanopatterningNanowiresScanning Probe MicroscopySilicon Photonics
@article{elnathan_optically_2021,
title = {Optically transparent vertical silicon nanowire arrays for live-cell imaging},
author = {Roey Elnathan and Andrew W. Holle and Jennifer Young and Marina A. George and Omri Heifler and Andriy Goychuk and Erwin Frey and Ralf Kemkemer and Joachim P. Spatz and Alon Kosloff and Fernando Patolsky and Nicolas H. Voelcker},
url = {https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-021-00795-7},
doi = {10.1186/s12951-021-00795-7},
issn = {1477-3155},
year = {2021},
date = {2021-12-01},
urldate = {2026-05-29},
journal = {Journal of Nanobiotechnology},
volume = {19},
number = {1},
pages = {51},
abstract = {Programmable nano-bio interfaces driven by tuneable vertically configured nanostructures have recently emerged as a powerful tool for cellular manipulations and interrogations. Such interfaces have strong potential for ground-breaking advances, particularly in cellular nanobiotechnology and mechanobiology. However, the opaque nature of many nanostructured surfaces makes non-destructive, live-cell characterization of cellular behavior on vertically aligned nanostructures challenging to observe. Here, a new nanofabrication route is proposed that enables harvesting of vertically aligned silicon (Si) nanowires and their subsequent transfer onto an optically transparent substrate, with high efficiency and without artefacts. We demonstrate the potential of this route for efficient live-cell phase contrast imaging and subsequent characterization of cells growing on vertically aligned Si nanowires. This approach provides the first opportunity to understand dynamic cellular responses to a cell-nanowire interface, and thus has the potential to inform the design of future nanoscale cellular manipulation technologies.},
keywords = {Biomaterials-Cells, Bionanoelectronics, Intracellular Delivery Techniques for Biomolecular Applications, Nanofabrication and Nanopatterning, Nanowires, Scanning Probe Microscopy, Silicon Photonics},
pubstate = {published},
tppubtype = {article}
}
Programmable nano-bio interfaces driven by tuneable vertically configured nanostructures have recently emerged as a powerful tool for cellular manipulations and interrogations. Such interfaces have strong potential for ground-breaking advances, particularly in cellular nanobiotechnology and mechanobiology. However, the opaque nature of many nanostructured surfaces makes non-destructive, live-cell characterization of cellular behavior on vertically aligned nanostructures challenging to observe. Here, a new nanofabrication route is proposed that enables harvesting of vertically aligned silicon (Si) nanowires and their subsequent transfer onto an optically transparent substrate, with high efficiency and without artefacts. We demonstrate the potential of this route for efficient live-cell phase contrast imaging and subsequent characterization of cells growing on vertically aligned Si nanowires. This approach provides the first opportunity to understand dynamic cellular responses to a cell-nanowire interface, and thus has the potential to inform the design of future nanoscale cellular manipulation technologies.
9
Surface-tension-induced budding drives alveologenesis in human mammary gland organoids
Pablo A. Fernández*; Benedikt Buchmann*; Andriy Goychuk*; Lisa K. Engelbrecht; Marion K. Raich; Christina H. Scheel†; Erwin Frey†; Andreas R. Bausch†
* Equal contribution † Corresponding author
In: Nature Physics, vol. 17, no. 10, pp. 1130–1136, 2021, ISSN: 1745-2473, 1745-2481.
Analytical TheoryBuddingCell MigrationCollective DynamicsMorphogenesisOrganoidsShape 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},
doi = {10.1038/s41567-021-01336-7},
issn = {1745-2473, 1745-2481},
year = {2021},
date = {2021-10-01},
urldate = {2021-10-01},
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.
8
A diffusiophoretic mechanism for ATP-driven transport without motor proteins Open access
Beatrice Ramm*; Andriy Goychuk*; Alena Khmelinskaia; Philipp Blumhardt; Hiromune Eto; Kristina A. Ganzinger; Erwin Frey†; Petra Schwille†
* Equal contribution † Corresponding author
In: Nature Physics, vol. 17, no. 7, pp. 850–858, 2021, ISSN: 1745-2473, 1745-2481.
Repository Abstract Links BibTeX
Analytical TheoryDiffusiophoresisNonequilibrium DynamicsPattern FormationTransport
In the press
@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},
doi = {10.1038/s41567-021-01213-3},
issn = {1745-2473, 1745-2481},
year = {2021},
date = {2021-07-01},
urldate = {2021-07-01},
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.
7
Tissue flow through pores: a computational study Preprint
Felix Kempf; Andriy Goychuk; Erwin Frey
2021.
Cell MigrationCell PolarizationCellular Potts ModelCollective DynamicsConfined MigrationSimulation
@preprint{kempf_tissue_2021,
title = {Tissue flow through pores: a computational study},
author = {Felix Kempf and Andriy Goychuk and Erwin Frey},
url = {http://biorxiv.org/lookup/doi/10.1101/2021.03.25.436985},
doi = {10.1101/2021.03.25.436985},
year = {2021},
date = {2021-03-01},
urldate = {2021-03-01},
publisher = {Biophysics},
abstract = {Cell migration is of major importance for the understanding of phenomena such as morphogenesis, cancer metastasis, or wound healing. In many of these situations cells are under external confinement. In this work we show by means of computer simulations with a Cellular Potts Model (CPM) that the presence of a bottleneck in an otherwise straight channel has a major influence on the internal organisation of an invading cellular monolayer and the motion of individual cells therein. Comparable to a glass or viscoelastic material, the cell sheet is found to exhibit features of both classical solids and classical fluids. The local ordering on average corresponds to a regular hexagonal lattice, while the relative motion of cells is unbounded. Compared to an unconstricted channel, we observe that a bottleneck perturbs the formation of regular hexagonal arrangements in the epithelial sheet and leads to pile-ups and backflow of cells near the entrance to the constriction, which also affects the overall invasion speed. The scale of these various phenomena depends on the dimensions of the different channel parts, as well as the shape of the funnel domain that connects wider to narrower regions.},
keywords = {Cell Migration, Cell Polarization, Cellular Potts Model, Collective Dynamics, Confined Migration, Simulation},
pubstate = {published},
tppubtype = {preprint}
}
Cell migration is of major importance for the understanding of phenomena such as morphogenesis, cancer metastasis, or wound healing. In many of these situations cells are under external confinement. In this work we show by means of computer simulations with a Cellular Potts Model (CPM) that the presence of a bottleneck in an otherwise straight channel has a major influence on the internal organisation of an invading cellular monolayer and the motion of individual cells therein. Comparable to a glass or viscoelastic material, the cell sheet is found to exhibit features of both classical solids and classical fluids. The local ordering on average corresponds to a regular hexagonal lattice, while the relative motion of cells is unbounded. Compared to an unconstricted channel, we observe that a bottleneck perturbs the formation of regular hexagonal arrangements in the epithelial sheet and leads to pile-ups and backflow of cells near the entrance to the constriction, which also affects the overall invasion speed. The scale of these various phenomena depends on the dimensions of the different channel parts, as well as the shape of the funnel domain that connects wider to narrower regions.
2020
6
Cell-Based Strain Remodeling of a Nonfibrous Matrix as an Organizing Principle for Vasculogenesis
Daniel Rüdiger; Kerstin Kick; Andriy Goychuk; Angelika M. Vollmar; Erwin Frey; Stefan Zahler
In: Cell Reports, vol. 32, no. 6, pp. 108015, 2020, ISSN: 22111247.
AngiogenesisEndothelialMatrigelPattern FormationStrain-Stiffening
@article{rudiger_cell-based_2020,
title = {Cell-Based Strain Remodeling of a Nonfibrous Matrix as an Organizing Principle for Vasculogenesis},
author = {Daniel Rüdiger and Kerstin Kick and Andriy Goychuk and Angelika M. Vollmar and Erwin Frey and Stefan Zahler},
url = {https://linkinghub.elsevier.com/retrieve/pii/S2211124720310007},
doi = {10.1016/j.celrep.2020.108015},
issn = {22111247},
year = {2020},
date = {2020-08-01},
urldate = {2026-05-29},
journal = {Cell Reports},
volume = {32},
number = {6},
pages = {108015},
abstract = {Endothelial tube formation on a reconstituted basement membrane (Matrigel) is a well-established in vitro model for studying the processes of angiogenesis and vasculogenesis. However, to date, the organizing principles that underlie the morphogenesis of this network and that shape the initial process of cells’ finding one another remain elusive. Here, we identify a mechanism that allows cells to form networks by mechanically reorganizing and stiffening their extracellular matrix, independent of chemical guidance cues. Interestingly, we find that this cellular self-organization strongly depends on the connectivity, plasticity, and topology of the surrounding matrix; cell contractility; and cell density. Cells rearrange the matrix and form bridges of matrix material that are stiffer than their surroundings, thus creating a durotactic track for the initiation of cell protrusions and cell-cell contacts. This contractility-based communication via strain stiffening and matrix rearrangement might be a general organizing principle during tissue development or regeneration.},
keywords = {Angiogenesis, Endothelial, Matrigel, Pattern Formation, Strain-Stiffening},
pubstate = {published},
tppubtype = {article}
}
Endothelial tube formation on a reconstituted basement membrane (Matrigel) is a well-established in vitro model for studying the processes of angiogenesis and vasculogenesis. However, to date, the organizing principles that underlie the morphogenesis of this network and that shape the initial process of cells’ finding one another remain elusive. Here, we identify a mechanism that allows cells to form networks by mechanically reorganizing and stiffening their extracellular matrix, independent of chemical guidance cues. Interestingly, we find that this cellular self-organization strongly depends on the connectivity, plasticity, and topology of the surrounding matrix; cell contractility; and cell density. Cells rearrange the matrix and form bridges of matrix material that are stiffer than their surroundings, thus creating a durotactic track for the initiation of cell protrusions and cell-cell contacts. This contractility-based communication via strain stiffening and matrix rearrangement might be a general organizing principle during tissue development or regeneration.
5
Quasi-periodic migration of single cells on short microlanes
Fang Zhou; Sophia A. Schaffer; Christoph Schreiber; Felix J. Segerer; Andriy Goychuk; Erwin Frey; Joachim O. Rädler
In: PLOS ONE, vol. 15, no. 4, pp. e0230679, 2020, ISSN: 1932-6203.
Actin PolymerizationActinsCell MigrationCellular Potts ModelCytoskeletonDepolarizationDirected Cell MigrationSimulationTransfectionVelocity
@article{zhou_quasi-periodic_2020,
title = {Quasi-periodic migration of single cells on short microlanes},
author = {Fang Zhou and Sophia A. Schaffer and Christoph Schreiber and Felix J. Segerer and Andriy Goychuk and Erwin Frey and Joachim O. Rädler},
editor = {Jordi Garcia-Ojalvo},
url = {https://dx.plos.org/10.1371/journal.pone.0230679},
doi = {10.1371/journal.pone.0230679},
issn = {1932-6203},
year = {2020},
date = {2020-04-01},
urldate = {2026-05-29},
journal = {PLOS ONE},
volume = {15},
number = {4},
pages = {e0230679},
abstract = {Cell migration on microlanes represents a suitable and simple platform for the exploration of the molecular mechanisms underlying cell cytoskeleton dynamics. Here, we report on the quasi-periodic movement of cells confined in stripe-shaped microlanes. We observe persistent polarized cell shapes and directed pole-to-pole motion within the microlanes. Cells depolarize at one end of a given microlane, followed by delayed repolarization towards the opposite end. We analyze cell motility via the spatial velocity distribution, the velocity frequency spectrum and the reversal time as a measure for depolarization and spontaneous repolarization of cells at the microlane ends. The frequent encounters of a boundary in the stripe geometry provides a robust framework for quantitative investigations of the cytoskeleton protrusion and repolarization dynamics. In a first advance to rigorously test physical models of cell migration, we find that the statistics of the cell migration is recapitulated by a Cellular Potts model with a minimal description of cytoskeleton dynamics. Using LifeAct-GFP transfected cells and microlanes with differently shaped ends, we show that the local deformation of the leading cell edge in response to the tip geometry can locally either amplify or quench actin polymerization, while leaving the average reversal times unaffected.},
keywords = {Actin Polymerization, Actins, Cell Migration, Cellular Potts Model, Cytoskeleton, Depolarization, Directed Cell Migration, Simulation, Transfection, Velocity},
pubstate = {published},
tppubtype = {article}
}
Cell migration on microlanes represents a suitable and simple platform for the exploration of the molecular mechanisms underlying cell cytoskeleton dynamics. Here, we report on the quasi-periodic movement of cells confined in stripe-shaped microlanes. We observe persistent polarized cell shapes and directed pole-to-pole motion within the microlanes. Cells depolarize at one end of a given microlane, followed by delayed repolarization towards the opposite end. We analyze cell motility via the spatial velocity distribution, the velocity frequency spectrum and the reversal time as a measure for depolarization and spontaneous repolarization of cells at the microlane ends. The frequent encounters of a boundary in the stripe geometry provides a robust framework for quantitative investigations of the cytoskeleton protrusion and repolarization dynamics. In a first advance to rigorously test physical models of cell migration, we find that the statistics of the cell migration is recapitulated by a Cellular Potts model with a minimal description of cytoskeleton dynamics. Using LifeAct-GFP transfected cells and microlanes with differently shaped ends, we show that the local deformation of the leading cell edge in response to the tip geometry can locally either amplify or quench actin polymerization, while leaving the average reversal times unaffected.
2019
4
Bridging the gap between single-cell migration and collective dynamics Open access
Florian Thüroff*; Andriy Goychuk*; Matthias Reiter; Erwin Frey
* Equal contribution
In: eLife, vol. 8, pp. e46842, 2019, ISSN: 2050-084X.
Cell MigrationCell PolarizationCellular Potts ModelCollective DynamicsSimulationWound Healing
@article{thuroff_bridging_2019,
title = {Bridging the gap between single-cell migration and collective dynamics},
author = {Florian Thüroff and Andriy Goychuk and Matthias Reiter and Erwin Frey},
doi = {10.7554/eLife.46842},
issn = {2050-084X},
year = {2019},
date = {2019-12-01},
urldate = {2019-12-01},
journal = {eLife},
volume = {8},
pages = {e46842},
abstract = {Motivated by the wealth of experimental data recently available, we present a cellular-automaton-based modeling framework focussing on high-level cell functions and their concerted effect on cellular migration patterns. Specifically, we formulate a coarse-grained description of cell polarity through self-regulated actin organization and its response to mechanical cues. Furthermore, we address the impact of cell adhesion on collective migration in cell cohorts. The model faithfully reproduces typical cell shapes and movements down to the level of single cells, yet allows for the efficient simulation of confluent tissues. In confined circular geometries, we find that specific properties of individual cells (polarizability; contractility) influence the emerging collective motion of small cell cohorts. Finally, we study the properties of expanding cellular monolayers (front morphology; stress and velocity distributions) at the level of extended tissues.},
keywords = {Cell Migration, Cell Polarization, Cellular Potts Model, Collective Dynamics, Simulation, Wound Healing},
pubstate = {published},
tppubtype = {article}
}
Motivated by the wealth of experimental data recently available, we present a cellular-automaton-based modeling framework focussing on high-level cell functions and their concerted effect on cellular migration patterns. Specifically, we formulate a coarse-grained description of cell polarity through self-regulated actin organization and its response to mechanical cues. Furthermore, we address the impact of cell adhesion on collective migration in cell cohorts. The model faithfully reproduces typical cell shapes and movements down to the level of single cells, yet allows for the efficient simulation of confluent tissues. In confined circular geometries, we find that specific properties of individual cells (polarizability; contractility) influence the emerging collective motion of small cell cohorts. Finally, we study the properties of expanding cellular monolayers (front morphology; stress and velocity distributions) at the level of extended tissues.
3
Protein Recruitment through Indirect Mechanochemical Interactions
Andriy Goychuk; Erwin Frey
In: Physical Review Letters, vol. 123, no. 17, pp. 178101, 2019, ISSN: 0031-9007, 1079-7114.
Analytical TheoryBiomolecular Self-AssemblyElastic DeformationFirst Passage ProblemsMean Field TheoryPattern FormationProtein-Membrane InteractionsProtein-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.
2018
2
Morphology and Motility of Cells on Soft Substrates Preprint
Andriy Goychuk; David B. Brückner; Andrew W. Holle; Joachim P. Spatz; Chase P. Broedersz; Erwin Frey
2018, (Version Number: 2).
Biological PhysicsCell BehaviorCell MigrationCell PolarizationCellular Potts ModelMechanobiologySimulationTraction Force
@preprint{goychuk_morphology_2018,
title = {Morphology and Motility of Cells on Soft Substrates},
author = {Andriy Goychuk and David B. Brückner and Andrew W. Holle and Joachim P. Spatz and Chase P. Broedersz and Erwin Frey},
url = {https://arxiv.org/abs/1808.00314},
doi = {10.48550/ARXIV.1808.00314},
year = {2018},
date = {2018-01-01},
urldate = {2018-01-01},
publisher = {arXiv},
abstract = {Recent experiments suggest that the interplay between cells and the mechanics of their substrate gives rise to a diversity of morphological and migrational behaviors. Here, we develop a Cellular Potts Model of polarizing cells on a visco-elastic substrate. We compare our model with experiments on endothelial cells plated on polyacrylamide hydrogels to constrain model parameters and test predictions. Our analysis reveals that morphology and migratory behavior are determined by an intricate interplay between cellular polarization and substrate strain gradients generated by traction forces exerted by cells (self-haptotaxis).},
note = {Version Number: 2},
keywords = {Biological Physics, Cell Behavior, Cell Migration, Cell Polarization, Cellular Potts Model, Mechanobiology, Simulation, Traction Force},
pubstate = {published},
tppubtype = {preprint}
}
Recent experiments suggest that the interplay between cells and the mechanics of their substrate gives rise to a diversity of morphological and migrational behaviors. Here, we develop a Cellular Potts Model of polarizing cells on a visco-elastic substrate. We compare our model with experiments on endothelial cells plated on polyacrylamide hydrogels to constrain model parameters and test predictions. Our analysis reveals that morphology and migratory behavior are determined by an intricate interplay between cellular polarization and substrate strain gradients generated by traction forces exerted by cells (self-haptotaxis).
2015
1
Stochastic Wilson–Cowan models of neuronal network dynamics with memory and delay
Igor Goychuk; Andriy Goychuk
In: New Journal of Physics, vol. 17, no. 4, pp. 045029, 2015, ISSN: 1367-2630.
AvalanchesNeural NetworksWilson-Cowan Models
@article{goychuk_stochastic_2015,
title = {Stochastic Wilson–Cowan models of neuronal network dynamics with memory and delay},
author = {Igor Goychuk and Andriy Goychuk},
url = {https://iopscience.iop.org/article/10.1088/1367-2630/17/4/045029},
doi = {10.1088/1367-2630/17/4/045029},
issn = {1367-2630},
year = {2015},
date = {2015-04-01},
urldate = {2026-05-29},
journal = {New Journal of Physics},
volume = {17},
number = {4},
pages = {045029},
abstract = {We consider a simple Markovian class of the stochastic Wilson–Cowan type models of neuronal network dynamics, which incorporates stochastic delay caused by the existence of a refractory period of neurons. From the point of view of the dynamics of the individual elements, we are dealing with a network of non-Markovian stochastic two-state oscillators with memory, which are coupled globally in a mean-field fashion. This interrelation of a higher-dimensional Markovian and lower-dimensional non-Markovian dynamics is discussed in its relevance to the general problem of the network dynamics of complex elements possessing memory. The simplest model of this class is provided by a three-state Markovian neuron with one refractory state, which causes firing delay with an exponentially decaying memory within the two-state reduced model. This basic model is used to study critical avalanche dynamics (the noise sustained criticality) in a balanced feedforward network consisting of the excitatory and inhibitory neurons. Such avalanches emerge due to the network size dependent noise (mesoscopic noise). Numerical simulations reveal an intermediate power law in the distribution of avalanche sizes with the critical exponent around −1.16. We show that this power law is robust upon a variation of the refractory time over several orders of magnitude. However, the avalanche time distribution is biexponential. It does not reflect any genuine power law dependence.},
keywords = {Avalanches, Neural Networks, Wilson-Cowan Models},
pubstate = {published},
tppubtype = {article}
}
We consider a simple Markovian class of the stochastic Wilson–Cowan type models of neuronal network dynamics, which incorporates stochastic delay caused by the existence of a refractory period of neurons. From the point of view of the dynamics of the individual elements, we are dealing with a network of non-Markovian stochastic two-state oscillators with memory, which are coupled globally in a mean-field fashion. This interrelation of a higher-dimensional Markovian and lower-dimensional non-Markovian dynamics is discussed in its relevance to the general problem of the network dynamics of complex elements possessing memory. The simplest model of this class is provided by a three-state Markovian neuron with one refractory state, which causes firing delay with an exponentially decaying memory within the two-state reduced model. This basic model is used to study critical avalanche dynamics (the noise sustained criticality) in a balanced feedforward network consisting of the excitatory and inhibitory neurons. Such avalanches emerge due to the network size dependent noise (mesoscopic noise). Numerical simulations reveal an intermediate power law in the distribution of avalanche sizes with the critical exponent around −1.16. We show that this power law is robust upon a variation of the refractory time over several orders of magnitude. However, the avalanche time distribution is biexponential. It does not reflect any genuine power law dependence.