- Open Access
Universal limiting behavior of reaction-diffusion systems with conservation laws
Phys. Rev. E 111, 065417 – Published 20 June, 2025
DOI: https://doi.org/10.1103/1bdc-1bjb
Abstract
Making sense of complex inhomogeneous systems composed of many interacting species is a grand challenge that pervades basically all natural sciences. Phase separation and pattern formation in reaction-diffusion systems have been largely studied as two separate paradigms. Here we show that in reaction-diffusion systems composed of many species, the presence of a conservation law constrains the evolution of the conserved quantity to be governed by a Cahn-Hilliard-like equation. This establishes a direct link with the paradigm of coexistence and recent “active” field theories. Hence, even for complex many-species systems a dramatically simplified but accurate description emerges over coarse spatiotemporal scales. Using the nullcline (the line of homogeneous steady states) as the central motif, we develop a geometrical framework which endows chemical space with a basis and suitable coordinates. This framework allows us to capture and understand the effect of eliminating fast nonconserved degrees of freedom and to explicitly construct coefficients of the coarse field theory. We expect that the theory we develop here will be particularly relevant to advance our understanding of biomolecular condensates.
Physics Subject Headings (PhySH)
Article Text
References (89)
- A. A. Hyman, C. A. Weber, and F. Jülicher, Liquid-liquid phase separation in biology, Annu. Rev. Cell Dev. Biol. 30, 39 (2014).
- S. F. Banani, H. O. Lee, A. A. Hyman, and M. K. Rosen, Biomolecular condensates: Organizers of cellular biochemistry, Nat. Rev. Mol. Cell Biol. 18, 285 (2017).
- C. A. Weber, D. Zwicker, F. Jülicher, and C. F. Lee, Physics of active emulsions, Rep. Prog. Phys. 82, 064601 (2019).
- H. Falahati and A. Haji-Akbari, Thermodynamically driven assemblies and liquid–liquid phase separations in biology, Soft Matter 15, 1135 (2019).
- W.-K. Cho, J.-H. Spille, M. Hecht, C. Lee, C. Li, V. Grube, and I. I. Cisse, Mediator and RNA polymerase II clusters associate in transcription-dependent condensates, Science 361, 412 (2018).
- D. Zwicker, R. Seyboldt, C. A. Weber, A. A. Hyman, and F. Jülicher, Growth and division of active droplets provides a model for protocells, Nat. Phys. 13, 408 (2017).
- J. D. Wurtz and C. F. Lee, Chemical-reaction-controlled phase separated drops: Formation, size selection, and coarsening, Phys. Rev. Lett. 120, 078102 (2018).
- C. F. Lee and J. D. Wurtz, Novel physics arising from phase transitions in biology, J. Phys. D: Appl. Phys. 52, 023001 (2019).
- P. C. Bressloff, Active suppression of Ostwald ripening: Beyond mean-field theory, Phys. Rev. E 101, 042804 (2020).
- J. Bauermann, S. Laha, P. M. McCall, F. Jülicher, and C. A. Weber, Chemical kinetics and mass action in coexisting phases, J. Am. Chem. Soc. 144, 19294 (2022).
- D. Zwicker, The intertwined physics of active chemical reactions and phase separation, Curr. Opin. Colloid Interface Sci. 61, 101606 (2022).
- A. M. Bergmann, J. Bauermann, G. Bartolucci, C. Donau, M. Stasi, A.-L. Holtmannspötter, F. Jülicher, C. A. Weber, and J. Boekhoven, Liquid spherical shells are a non-equilibrium steady state of active droplets, Nat. Commun. 14, 6552 (2023).
- A. Turing, The chemical basis of morphogenesis, Phil. Trans. R. Soc. Lond. B 237, 37 (1952).
- P. Gray and S. K. Scott, Autocatalytic reactions in the isothermal, continuous stirred tank reactor: Isolas and other forms of multistability, Chem. Eng. Sci. 38, 29 (1983).
- P. Gray and S. K. Scott, Autocatalytic reactions in the isothermal, continuous stirred tank reactor: Oscillations and instabilities in the system A + 2B 3B; B C, Chem. Eng. Sci. 39, 1087 (1984).
- I. S. Aranson and L. Kramer, The world of the complex Ginzburg-Landau equation, Rev. Mod. Phys. 74, 99 (2002).
- J. Swift and P. C. Hohenberg, Hydrodynamic fluctuations at the convective instability, Phys. Rev. A 15, 319 (1977).
- S. C. Glotzer, E. A. Di Marzio, and M. Muthukumar, Reaction-controlled morphology of phase-separating mixtures, Phys. Rev. Lett. 74, 2034 (1995).
- Q. Ouyang, J. Boissonade, J. Roux, and P. De Kepper, Sustained reaction-diffusion structures in an open reactor, Phys. Lett. A 134, 282 (1989).
- V. Castets, E. Dulos, J. Boissonade, and P. De Kepper, Experimental evidence of a sustained standing Turing-type nonequilibrium chemical pattern, Phys. Rev. Lett. 64, 2953 (1990).
- S. Kondo and T. Miura, Reaction-diffusion model as a framework for understanding biological pattern formation, Science 329, 1616 (2010).
- S. Kondo, M. Watanabe, and S. Miyazawa, Studies of Turing pattern formation in zebrafish skin, Phil. Trans. R. Soc. A. 379, 20200274 (2021).
- M. Otsuji, S. Ishihara, C. Co, K. Kaibuchi, A. Mochizuki, and S. Kuroda, A mass conserved reaction–diffusion system captures properties of cell polarity, PLoS Comput. Biol. 3, e108 (2007).
- S. J. Altschuler, S. B. Angenent, Y. Wang, and L. F. Wu, On the spontaneous emergence of cell polarity, Nature (London) 454, 886 (2008).
- A. B. Goryachev and A. V. Pokhilko, Dynamics of Cdc42 network embodies a Turing-type mechanism of yeast cell polarity, FEBS Lett. 582, 1437 (2008).
- Y. Mori, A. Jilkine, and L. Edelstein-Keshet, Wave-pinning and cell polarity from a bistable reaction-diffusion system, Biophys. J. 94, 3684 (2008).
- A. Jilkine and L. Edelstein-Keshet, A comparison of mathematical models for polarization of single eukaryotic cells in response to guided cues, PLoS Comput. Biol. 7, e1001121 (2011).
- L. Edelstein-Keshet, W. R. Holmes, M. Zajac, and M. Dutot, From simple to detailed models for cell polarization, Phil. Trans. R. Soc. B 368, 20130003 (2013).
- P. K. Trong, E. M. Nicola, N. W. Goehring, K. V. Kumar, and S. W. Grill, Parameter-space topology of models for cell polarity, New J. Phys. 16, 065009 (2014).
- S. Seirin Lee and T. Shibata, Self-organization and advective transport in the cell polarity formation for asymmetric cell division, J. Theor. Biol. 382, 1 (2015).
- J.-G. Chiou, S. A. Ramirez, T. C. Elston, T. P. Witelski, D. G. Schaeffer, and D. J. Lew, Principles that govern competition or co-existence in Rho-GTPase driven polarization, PLoS Comput. Biol. 14, e1006095 (2018).
- F. Bergmann, L. Rapp, and W. Zimmermann, Active phase separation: A universal approach, Phys. Rev. E 98, 020603(R) (2018).
- F. Bergmann and W. Zimmermann, On system-spanning demixing properties of cell polarization, PLOS One 14, e0218328 (2019).
- P. W. Miller, D. Fortunato, M. Novaga, S. Y. Shvartsman, and C. B. Muratov, Generation and motion of interfaces in a mass-conserving reaction-diffusion system, SIAM J. Appl. Dyn. Syst. 22, 2408 (2023).
- I. Prigogine and G. Nicolis, On symmetry-breaking instabilities in dissipative systems, J. Chem. Phys. 46, 3542 (1967).
- I. Prigogine and R. Lefever, Symmetry breaking instabilities in dissipative systems, II, J. Chem. Phys. 48, 1695 (1968).
- U. Seifert, Stochastic thermodynamics, fluctuation theorems and molecular machines, Rep. Prog. Phys. 75, 126001 (2012).
- S. Ramaswamy, The mechanics and statistics of active matter, Annu. Rev. Condens. Matter Phys. 1, 323 (2010).
- M. C. Marchetti, J. F. Joanny, S. Ramaswamy, T. B. Liverpool, J. Prost, M. Rao, and R. A. Simha, Hydrodynamics of soft active matter, Rev. Mod. Phys. 85, 1143 (2013).
- C. Bechinger, R. Di Leonardo, H. Löwen, C. Reichhardt, G. Volpe, and G. Volpe, Active particles in complex and crowded environments, Rev. Mod. Phys. 88, 045006 (2016).
- R. Milo and R. Phillips, Cell Biology by the Numbers (Garland Science, New York, 2016).
- E. Balleza, J. M. Kim, and P. Cluzel, Systematic characterization of maturation time of fluorescent proteins in living cells, Nat. Methods 15, 47 (2018).
- X. Han, D. Yu, R. Gu, Y. Jia, Q. Wang, A. Jaganathan, X. Yang, M. Yu, N. Babault, C. Zhao, H. Yi, Q. Zhang, M.-M. Zhou, and L. Zeng, Roles of the BRD4 short isoform in phase separation and active gene transcription, Nat. Struct. Mol. Biol. 27, 333 (2020).
- R. Rao and M. Esposito, Nonequilibrium thermodynamics of chemical reaction networks: Wisdom from stochastic thermodynamics, Phys. Rev. X 6, 041064 (2016).
- K.-D. Willamowski and O. E. Rössler, Irregular oscillations in a realistic abstract quadratic mass action system, Zeitschr. Naturforsch. A 35, 317 (1980).
- J. Halatek and E. Frey, Rethinking pattern formation in reaction–diffusion systems, Nat. Phys. 14, 507 (2018).
- F. Brauns, J. Halatek, and E. Frey, Phase-space geometry of mass-conserving reaction-diffusion dynamics, Phys. Rev. X 10, 041036 (2020).
- F. Brauns, H. Weyer, J. Halatek, J. Yoon, and E. Frey, Wavelength selection by interrupted coarsening in reaction-diffusion systems, Phys. Rev. Lett. 126, 104101 (2021).
- J. Mallet-Paret and G. R. Sell, Inertial manifolds for reaction diffusion equations in higher space dimensions, J. Am. Math. Soc. 1, 805 (1988).
- M. R. Roussel and S. J. Fraser, Invariant manifold methods for metabolic model reduction, Chaos 11, 196 (2001).
- M. E. Cates and J. Tailleur, Motility-induced phase separation, Annu. Rev. Condens. Matter Phys. 6, 219 (2015).
- J. W. Cahn and J. E. Hilliard, Free energy of a nonuniform system. I. Interfacial free energy, J. Chem. Phys. 28, 258 (1958).
- P. C. Hohenberg and B. I. Halperin, Theory of dynamic critical phenomena, Rev. Mod. Phys. 49, 435 (1977).
- C. Nardini, É. Fodor, E. Tjhung, F. van Wijland, J. Tailleur, and M. E. Cates, Entropy production in field theories without time-reversal symmetry: Quantifying the non-equilibrium character of active matter, Phys. Rev. X 7, 021007 (2017).
- E. Tjhung, C. Nardini, and M. E. Cates, Cluster phases and bubbly phase separation in active fluids: Reversal of the Ostwald process, Phys. Rev. X 8, 031080 (2018).
- A. J. Bray, Theory of phase-ordering kinetics, Adv. Phys. 51, 481 (2002).
- T. Speck, J. Bialké, A. M. Menzel, and H. Löwen, Effective Cahn-Hilliard equation for the phase separation of active Brownian particles, Phys. Rev. Lett. 112, 218304 (2014).
- J. Stenhammar, A. Tiribocchi, R. J. Allen, D. Marenduzzo, and M. E. Cates, Continuum theory of phase separation kinetics for active Brownian particles, Phys. Rev. Lett. 111, 145702 (2013).
- R. Wittkowski, A. Tiribocchi, J. Stenhammar, R. J. Allen, D. Marenduzzo, and M. E. Cates, Scalar field theory for active-particle phase separation, Nat. Commun. 5, 4351 (2014).
- G. Fausti, E. Tjhung, M. E. Cates, and C. Nardini, Capillary interfacial tension in active phase separation, Phys. Rev. Lett. 127, 068001 (2021).
- F. Caballero, C. Nardini, and M. E. Cates, From bulk to microphase separation in scalar active matter: A perturbative renormalization group analysis, J. Stat. Mech. (2018) 123208.
- M. E. Cates and C. Nardini, Classical nucleation theory for active fluid phase separation, Phys. Rev. Lett. 130, 098203 (2023).
- Y. Zheng, M. A. Klatt, and H. Löwen, Universal hyperuniformity in active field theories, Phys. Rev. Res. 6, L032056 (2023).
- M. Kourbane-Houssene, C. Erignoux, T. Bodineau, and J. Tailleur, Exact hydrodynamic description of active lattice gases, Phys. Rev. Lett. 120, 268003 (2018).
- T. Speck, Critical behavior of active Brownian particles: Connection to field theories, Phys. Rev. E 105, 064601 (2022).
- M. te Vrugt, J. Bickmann, and R. Wittkowski, How to derive a predictive field theory for active Brownian particles: A step-by-step tutorial, J. Phys.: Condens. Matter 35, 313001 (2023).
- E. Kalz, A. Sharma, and R. Metzler, Field-theory of active chiral hard disks: A first-principles approach to steric interactions, J. Phys. A: Math. Theor. 57, 265002 (2024).
- H. Alston, A. O. Parry, R. Voituriez, and T. Bertrand, Intermittent attractive interactions lead to microphase separation in nonmotile active matter, Phys. Rev. E 106, 034603 (2022).
- J.-P. Hansen and I. R. McDonald, Theory of Simple Liquids with Applications to Soft Matter, 4th ed. (Elsevier, Amsterdam, 2013).
- D. S. Dean, Langevin equation for the density of a system of interacting Langevin processes, J. Phys. A: Math. Gen. 29, L613 (1996).
- A. J. Archer and R. Evans, Dynamical density functional theory and its application to spinodal decomposition, J. Chem. Phys. 121, 4246 (2004).
- G. Falasco, R. Rao, and M. Esposito, Information thermodynamics of Turing patterns, Phys. Rev. Lett. 121, 108301 (2018).
- H. V. Helmholtz, Über die physikalische Bedeutung des Prinicips der kleinsten Wirkung, Crelles J. 1887, 137 (1887).
- E. Tonti, Variational formulation of nonlinear differential equations (I), Bull. Acad. Roy. Belg. 55, 137 (1969).
- A. P. Solon, J. Stenhammar, M. E. Cates, Y. Kafri, and J. Tailleur, Generalized thermodynamics of phase equilibria in scalar active matter, Phys. Rev. E 97, 020602(R) (2018).
- M. C. Cross and P. C. Hohenberg, Pattern formation outside of equilibrium, Rev. Mod. Phys. 65, 851 (1993).
- R. C. Desai and R. Kapral, Dynamics of Self-organized and Self-assembled Structures (Cambridge University Press, Cambridge, UK, 2009).
- Y. Kuramoto and T. Tsuzuki, On the formation of dissipative structures in reaction-diffusion systems: Reductive perturbation approach, Prog. Theor. Phys. 54, 687 (1975).
- Y. Kuramoto and T. Tsuzuki, Persistent propagation of concentration waves in dissipative media far from thermal equilibrium, Prog. Theor. Phys. 55, 356 (1976).
- T. Ohta, M. Mimura, and R. Kobayashi, Higher-dimensional localized patterns in excitable media, Physica D 34, 115 (1989).
- D. M. Petrich and R. E. Goldstein, Nonlocal contour dynamics model for chemical front motion, Phys. Rev. Lett. 72, 1120 (1994).
- G. Drazer and H. S. Wio, Nonequilibrium potential approach: Local and global stability of stationary patterns in an activator-inhibitor system with fast inhibition, Physica A 240, 571 (1997).
- W. R. Holmes, A. E. Carlsson, and L. Edelstein-Keshet, Regimes of wave type patterning driven by refractory actin feedback: Transition from static polarization to dynamic wave behaviour, Phys. Biol. 9, 046005 (2012).
- C. Gai, D. Iron, and T. Kolokolnikov, Localized outbreaks in an S-I-R model with diffusion, J. Math. Biol. 80, 1389 (2020).
- S. M. Murray and V. Sourjik, Self-organization and positioning of bacterial protein clusters, Nat. Phys 13, 1006 (2017).
- M. W. Cotton, R. Golestanian, and J. Agudo-Canalejo, Catalysis-induced phase separation and autoregulation of enzymatic activity, Phys. Rev. Lett. 129, 158101 (2022).
- B. Q. Lu, R. Evans, and M. Telo Da Gama, The form of the density profile at a liquid-gas interface: Dependence on the intermolecular potential, Mol. Phys. 55, 1319 (1985).
- J. F. Robinson, reactGPU a package to simulate reaction-diffusion systems with CUDA acceleration, GitHub repository (2024), https://github.com/tranqui/reactGPU.
- G. B. Folland, How to integrate a polynomial over a sphere, Am. Math. Mon. 108, 446 (2001).