Reuse & Permissions

It is not necessary to obtain permission to reuse this article or its components as it is available under the terms of the Creative Commons Attribution 4.0 International license. This license permits unrestricted use, distribution, and reproduction in any medium, provided attribution to the author(s) and the published article's title, journal citation, and DOI are maintained. Please note that some figures may have been included with permission from other third parties. It is your responsibility to obtain the proper permission from the rights holder directly for these figures.

Export citation

Export citation

Choose format for download:

Download Citation
  • Open Access

Anomalous diffusion in coupled viscoelastic media: A fractional Langevin equation approach

Chan Lim1 and Jae-Hyung Jeon1,2,3,*

  • *Contact author: jeonjh@postech.ac.kr

Phys. Rev. Research 7, 043356 – Published 31 December, 2025

DOI: https://doi.org/10.1103/thv9-s9mq

Abstract

Anomalous diffusion often arises in complex environments where viscoelastic or crowded conditions influence particle motion. In many biological and soft-matter systems, distinct components of the medium exhibit unique viscoelastic responses, resulting in time-dependent changes in the observed diffusion exponents. Here, we develop a theoretical model of two particles, each embedded in a distinct viscoelastic medium, and coupled via a harmonic potential. By formulating and solving a system of coupled fractional Langevin equations (FLEs) with memory exponents 0<α<β≤1, we uncover rich transient anomalous diffusion phenomena arising from the interplay of memory kernels and bilinear coupling. Notably, we identify “recovery dynamics,” where a subdiffusive particle (α) transiently accelerates and eventually regains its intrinsic long-time mobility. This recovery emerges only when memory exponents differ (α<β), whereas identical exponents (α=β) suppress recovery. Our FLE models are further validated in comparison with Langevin dynamics simulations of polymer-based real systems. Our theoretical predictions offer insight into experimentally observed transient anomalous diffusions, such as polymer-protein complexes and cross-linked cytoskeletal networks, highlighting the critical role of memory heterogeneity and mechanical interactions in biological anomalous diffusion.

View figure in article

Physics Subject Headings (PhySH)

Article Text

References (86)

  1. R. Metzler, J.-H. Jeon, A. G. Cherstvy, and E. Barkai, Anomalous diffusion models and their properties: Non-stationarity, non-ergodicity, and ageing at the centenary of single particle tracking, Phys. Chem. Chem. Phys. 16, 24128 (2014).
  2. M. Baggioli, G. La Nave, and P. W. Phillips, Anomalous diffusion and Noether's second theorem, Phys. Rev. E 103, 032115 (2021).
  3. G. W. Ford, M. Kac, and P. Mazur, Statistical mechanics of assemblies of coupled oscillators, J. Math. Phys. 6, 504 (1965).
  4. H. Mori, Transport, collective motion, and Brownian motion, Prog. Theor. Phys. 33, 423 (1965).
  5. R. Zwanzig, Nonlinear generalized Langevin equations, J. Stat. Phys. 9, 215 (1973).
  6. R. Kubo, The fluctuation-dissipation theorem, Rep. Prog. Phys. 29, 255 (1966).
  7. E. Lutz, Fractional Langevin equation, Phys. Rev. E 64, 051106 (2001).
  8. I. Goychuk, Viscoelastic subdiffusion: From anomalous to normal, Phys. Rev. E 80, 046125 (2009).
  9. I. Goychuk, Viscoelastic subdiffusion: Generalized Langevin equation approach, in Advances in Chemical Physics (John Wiley & Sons, Ltd., New York, NY, 2012), pp. 187–253.
  10. S. C. Kou and X. S. Xie, Generalized Langevin equation with fractional Gaussian noise: Subdiffusion within a single protein molecule, Phys. Rev. Lett. 93, 180603 (2004).
  11. W. Min, G. Luo, B. J. Cherayil, S. C. Kou, and X. S. Xie, Observation of a power-law memory kernel for fluctuations within a single protein molecule, Phys. Rev. Lett. 94, 198302 (2005).
  12. B. Fabry, G. N. Maksym, J. P. Butler, M. Glogauer, D. Navajas, and J. J. Fredberg, Scaling the microrheology of living cells, Phys. Rev. Lett. 87, 148102 (2001).
  13. C. Wilhelm, Out-of-equilibrium microrheology inside living cells, Phys. Rev. Lett. 101, 028101 (2008).
  14. M. Guo, A. J. Ehrlicher, M. H. Jensen, M. Renz, J. R. Moore, R. D. Goldman, J. Lippincott-Schwartz, F. C. Mackintosh, and D. A. Weitz, Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy, Cell 158, 822 (2014).
  15. S. C. Weber, A. J. Spakowitz, and J. A. Theriot, Bacterial chromosomal loci move subdiffusively through a viscoelastic cytoplasm, Phys. Rev. Lett. 104, 238102 (2010).
  16. T. J. Lampo, N. J. Kuwada, P. A. Wiggins, and A. J. Spakowitz, Physical modeling of chromosome segregation in Escherichia coli reveals impact of force and DNA relaxation, Biophys. J. 108, 146 (2015).
  17. T. G. Mason, T. Gisler, K. Kroy, E. Frey, and D. A. Weitz, Rheology of F-actin solutions determined from thermally driven tracer motion, J. Rheol. 44, 917 (2000).
  18. T. Gisler and D. A. Weitz, Scaling of the microrheology of semidilute F-actin solutions, Phys. Rev. Lett. 82, 1606 (1999).
  19. B. Schnurr, F. Gittes, F. C. MacKintosh, and C. F. Schmidt, Determining microscopic viscoelasticity in flexible and semiflexible polymer networks from thermal fluctuations, Macromolecules 30, 7781 (1997).
  20. B. R. Dasgupta, S.-Y. Tee, J. C. Crocker, B. J. Frisken, and D. A. Weitz, Microrheology of polyethylene oxide using diffusing wave spectroscopy and single scattering, Phys. Rev. E 65, 051505 (2002).
  21. M. Caputo, Linear models of dissipation whose Q is almost frequency independent—II, Geophys. J. Int. 13, 529 (1967).
  22. E. C. de Oliveira and J. A. Tenreiro Machado, A review of definitions for fractional derivatives and integral, Math. Probl. Eng. 2014, 238459 (2014).
  23. T. G. Mason and D. A. Weitz, Optical measurements of frequency-dependent linear viscoelastic moduli of complex fluids, Phys. Rev. Lett. 74, 1250 (1995).
  24. I. Goychuk and P. Hänggi, Anomalous escape governed by thermal 1/f noise, Phys. Rev. Lett. 99, 200601 (2007).
  25. A. Taloni, A. Chechkin, and J. Klafter, Generalized elastic model yields a fractional Langevin equation description, Phys. Rev. Lett. 104, 160602 (2010).
  26. D. Panja, Anomalous polymer dynamics is non-Markovian: Memory effects and the generalized Langevin equation formulation, J. Stat. Mech. (2010) P06011.
  27. L. Lizana, T. Ambjörnsson, A. Taloni, E. Barkai, and M. A. Lomholt, Foundation of fractional Langevin equation: Harmonization of a many-body problem, Phys. Rev. E 81, 051118 (2010).
  28. H. Vandebroek and C. Vanderzande, On the generalized Langevin equation for a Rouse bead in a nonequilibrium bath, J. Stat. Phys. 167, 14 (2017).
  29. C. Maes and S. R. Thomas, From Langevin to generalized Langevin equations for the nonequilibrium Rouse model, Phys. Rev. E 87, 022145 (2013).
  30. S. Shinkai, S. Onami, and T. Miyaguchi, Generalized Langevin dynamics for single beads in linear elastic networks, Phys. Rev. E 110, 044136 (2024).
  31. H.-T. Han, S. Joo, T. Sakaue, and J.-H. Jeon, Nonequilibrium diffusion of active particles bound to a semiflexible polymer network: Simulations and fractional Langevin equation, J. Chem. Phys. 159, 024901 (2023).
  32. X. Durang, C. Lim, and J.-H. Jeon, Generalized Langevin equation for a tagged monomer in a Gaussian semiflexible polymer, J. Chem. Phys. 161, 244906 (2024).
  33. T. Sakaue, Memory effect and fluctuating anomalous dynamics of a tagged monomer, Phys. Rev. E 87, 040601 (2013).
  34. J. Kappler, F. Noé, and R. R. Netz, Cyclization and relaxation dynamics of finite-length collapsed self-avoiding polymers, Phys. Rev. Lett. 122, 067801 (2019).
  35. D. Panja, Generalized Langevin equation formulation for anomalous polymer dynamics, J. Stat. Mech. (2010) L02001.
  36. A. Rigato, A. Miyagi, S. Scheuring, and F. Rico, High-frequency microrheology reveals cytoskeleton dynamics in living cells, Nat. Phys. 13, 771 (2017).
  37. J.-H. Jeon, H. M.-S. Monne, M. Javanainen, and R. Metzler, Anomalous diffusion of phospholipids and cholesterols in a lipid bilayer and its origins, Phys. Rev. Lett. 109, 188103 (2012).
  38. E. Yamamoto, T. Akimoto, A. C. Kalli, K. Yasuoka, and M. S. P. Sansom, Dynamic interactions between a membrane binding protein and lipids induce fluctuating diffusivity, Sci. Adv. 3, e1601871 (2017).
  39. F. Watanabe, T. Akimoto, R. B. Best, K. Lindorff-Larsen, R. Metzler, and E. Yamamoto, Diffusion of intrinsically disordered proteins within viscoelastic membraneless droplets, Phys. Rev. Res. 7, 043117 (2025).
  40. T. Germier, S. Kocanova, N. Walther, A. Bancaud, H. A. Shaban, H. Sellou, A. Z. Politi, J. Ellenberg, F. Gallardo, and K. Bystricky, Real-time imaging of a single gene reveals transcription-initiated local confinement, Biophys. J. 113, 1383 (2017).
  41. A. Zidovska, D. A. Weitz, and T. J. Mitchison, Micron-scale coherence in interphase chromatin dynamics, Proc. Natl. Acad. Sci. USA 110, 15555 (2013).
  42. I. Bronstein, Y. Israel, E. Kepten, S. Mai, Y. Shav-Tal, E. Barkai, and Y. Garini, Transient anomalous diffusion of telomeres in the nucleus of mammalian cells, Phys. Rev. Lett. 103, 018102 (2009).
  43. I. Bronshtein, E. Kepten, I. Kanter, S. Berezin, M. Lindner, A. B. Redwood, S. Mai, S. Gonzalo, R. Foisner, Y. Shav-Tal, and Y. Garini, Loss of lamin A function increases chromatin dynamics in the nuclear interior, Nat. Commun. 6, 8044 (2015).
  44. S. S. Ashwin, T. Nozaki, K. Maeshima, and M. Sasai, Organization of fast and slow chromatin revealed by single-nucleosome dynamics, Proc. Natl. Acad. Sci. USA 116, 19939 (2019).
  45. N. Khanna, Y. Zhang, J. S. Lucas, O. K. Dudko, and C. Murre, Chromosome dynamics near the sol-gel phase transition dictate the timing of remote genomic interactions, Nat. Commun. 10, 2771 (2019).
  46. V. Levi, Q. Ruan, M. Plutz, A. S. Belmont, and E. Gratton, Chromatin dynamics in interphase cells revealed by tracking in a two-photon excitation microscope, Biophys. J. 89, 4275 (2005).
  47. B. D. Hoffman, G. Massiera, K. M. Van Citters, and J. C. Crocker, The consensus mechanics of cultured mammalian cells, Proc. Natl. Acad. Sci. USA 103, 10259 (2006).
  48. M. Otten, A. Nandi, D. Arcizet, M. Gorelashvili, B. Lindner, and D. Heinrich, Local motion analysis reveals impact of the dynamic cytoskeleton on intracellular subdiffusion, Biophys. J. 102, 758 (2012).
  49. P. Annibale and E. Gratton, Single cell visualization of transcription kinetics variance of highly mobile identical genes using 3D nanoimaging, Sci. Rep. 5, 9258 (2015).
  50. M. Mak, S. Anderson, M. C. McDonough, F. Spill, J. E. Kim, A. Boussommier-Calleja, M. H. Zaman, and R. D. Kamm, Integrated analysis of intracellular dynamics of menainv cancer cells in a 3D matrix, Biophys. J. 112, 1874 (2017).
  51. S. S. Rogers, T. A. Waigh, and J. R. Lu, Intracellular microrheology of motile Amoeba proteus, Biophys. J. 94, 3313 (2008).
  52. E. Lee, D. Kim, Y. H. Song, K. Shin, S. Song, M. Lee, Y. Goh, M. H. Lim, J.-H. Kim, J. Sung, and K. T. Lee, Real-time tracking of vesicles in living cells reveals that tau-hyperphosphorylation suppresses unidirectional transport by motor proteins, Chem. Biomed. Imaging 2, 362 (2024).
  53. K. Murase, T. Fujiwara, Y. Umemura, K. Suzuki, R. Iino, H. Yamashita, M. Saito, H. Murakoshi, K. Ritchie, and A. Kusumi, Ultrafine membrane compartments for molecular diffusion as revealed by single molecule techniques, Biophys. J. 86, 4075 (2004).
  54. K. Suzuki, K. Ritchie, E. Kajikawa, T. Fujiwara, and A. Kusumi, Rapid hop diffusion of a G-protein-coupled receptor in the plasma membrane as revealed by single-molecule techniques, Biophys. J. 88, 3659 (2005).
  55. D. M. Wulstein, K. E. Regan, J. Garamella, R. J. McGorty, and R. M. Robertson-Anderson, Topology-dependent anomalous dynamics of ring and linear DNA are sensitive to cytoskeleton crosslinking, Sci. Adv. 5, eaay5912 (2019).
  56. J. Garamella, K. Regan, G. Aguirre, R. J. McGorty, and R. M. Robertson-Anderson, Anomalous and heterogeneous DNA transport in biomimetic cytoskeleton networks, Soft Matter 16, 6344 (2020).
  57. S. J. Anderson, J. Garamella, S. Adalbert, R. J. McGorty, and R. M. Robertson-Anderson, Subtle changes in crosslinking drive diverse anomalous transport characteristics in actin–microtubule networks, Soft Matter 17, 4375 (2021).
  58. G. Lee, G. Leech, M. J. Rust, M. Das, R. J. McGorty, J. L. Ross, and R. M. Robertson-Anderson, Myosin-driven actin-microtubule networks exhibit self-organized contractile dynamics, Sci. Adv. 7, eabe4334 (2021).
  59. J. Y. Sheung, J. Garamella, S. K. Kahl, B. Y. Lee, R. J. McGorty, and R. M. Robertson-Anderson, Motor-driven advection competes with crowding to drive spatiotemporally heterogeneous transport in cytoskeleton composites, Front. Phys. 10, 1055441 (2022).
  60. B. A. Krajina, B. L. LeSavage, J. G. Roth, A. W. Zhu, P. C. Cai, A. J. Spakowitz, and S. C. Heilshorn, Microrheology reveals simultaneous cell-mediated matrix stiffening and fluidization that underlie breast cancer invasion, Sci. Adv. 7, eabe1969 (2021).
  61. E. L. Baker, R. T. Bonnecaze, and M. H. Zaman, Extracellular matrix stiffness and architecture govern intracellular rheology in cancer, Biophys. J. 97, 1013 (2009).
  62. G. Higgins, F. Higgins, J. Peres, D. M. Lang, T. Abdalrahman, M. H. Zaman, S. Prince, and T. Franz, Intracellular mechanics and TBX3 expression jointly dictate the spreading mode of melanoma cells in 3D environments, Exp. Cell Res. 428, 113633 (2023).
  63. F. Spitz and E. E. M. Furlong, Transcription factors: From enhancer binding to developmental control, Nat. Rev. Genet. 13, 613 (2012).
  64. C. R. Clapier, J. Iwasa, B. R. Cairns, and C. L. Peterson, Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes, Nat. Rev. Mol. Cell Biol. 18, 407 (2017).
  65. Q. Su, S. Mehta, and J. Zhang, Liquid-liquid phase separation: Orchestrating cell signaling through time and space, Mol. Cell 81, 4137 (2021).
  66. T. Hirose, K. Ninomiya, S. Nakagawa, and T. Yamazaki, A guide to membraneless organelles and their various roles in gene regulation, Nat. Rev. Mol. Cell Biol. 24, 288 (2023).
  67. S. N. Ricketts, J. L. Ross, and R. M. Robertson-Anderson, Co-entangled actin-microtubule composites exhibit tunable stiffness and power-law stress relaxation, Biophys. J. 115, 1055 (2018).
  68. F. Gittes, B. Mickey, J. Nettleton, and J. Howard, Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape., J. Cell Biol. 120, 923 (1993).
  69. M. Kikumoto, M. Kurachi, V. Tosa, and H. Tashiro, Flexural rigidity of individual microtubules measured by a buckling force with optical traps, Biophys. J. 90, 1687 (2006).
  70. F. Huber, A. Boire, M. P. López, and G. H. Koenderink, Cytoskeletal crosstalk: When three different personalities team up, Curr. Opin. Cell Biol. 32, 39 (2015).
  71. M. Schulz, S. Stepanow, and S. Trimper, Two harmonically coupled Brownian particles in random media, Europhys. Lett. 54, 424 (2001).
  72. H. J. Haubold, A. M. Mathai, and R. K. Saxena, Mittag-Leffler functions and their applications, J. Appl. Math. 2011, 298628 (2011).
  73. F. Mainardi, Why the Mittag-Leffler function can be considered the queen function of the fractional calculus? Entropy 22, 1359 (2020).
  74. H. Stehfest, Algorithm 368: Numerical inversion of Laplace transforms [D5], Commun. ACM 13, 47 (1970).
  75. J.-H. Jeon and R. Metzler, Inequivalence of time and ensemble averages in ergodic systems: Exponential versus power-law relaxation in confinement, Phys. Rev. E 85, 021147 (2012).
  76. K. Rippe and A. Papantonis, RNA polymerase II transcription compartments—from factories to condensates, Nat. Rev. Genet. 26, 775 (2025).
  77. E. Alghoul, J. Basbous, and A. Constantinou, Compartmentalization of the DNA damage response: Mechanisms and functions, DNA Repair 128, 103524 (2023).
  78. A. G. Larson, D. Elnatan, M. M. Keenen, M. J. Trnka, J. B. Johnston, A. L. Burlingame, D. A. Agard, S. Redding, and G. J. Narlikar, Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin, Nature (London) 547, 236 (2017).
  79. M. Wachsmuth, W. Waldeck, and J. Langowski, Anomalous diffusion of fluorescent probes inside living cell nuclei investigated by spatially-resolved fluorescence correlation spectroscopy, J. Mol. Biol. 298, 677 (2000).
  80. A. Bancaud, S. Huet, N. Daigle, J. Mozziconacci, J. Beaudouin, and J. Ellenberg, Molecular crowding affects diffusion and binding of nuclear proteins in heterochromatin and reveals the fractal organization of chromatin, EMBO J. 28, 3785 (2009).
  81. M. K. Daddysman and C. J. Fecko, Revisiting point FRAP to quantitatively characterize anomalous diffusion in live cells, J. Phys. Chem. B 117, 1241 (2013).
  82. L. Meng, R. Zhang, L. Yu, and H. Wang, Tempered anomalous dynamics of globally coupled harmonic oscillators in the fluctuating potential field: Stability, synchronism, and collective behaviors, Eur. Phys. J. Plus 139, 63 (2024).
  83. M. C. Lim and M. J.-H. Jeon, Simulation files are freely available at https://github.com/chanlimresearch/coupled-FLE-polymer-sim.
  84. M. V. Tamm, L. I. Nazarov, A. A. Gavrilov, and A. V. Chertovich, Anomalous diffusion in fractal globules, Phys. Rev. Lett. 114, 178102 (2015).
  85. E. Vanden-Eijnden and G. Ciccotti, Second-order integrators for Langevin equations with holonomic constraints, Chem. Phys. Lett. 429, 310 (2006).
  86. R. G. Winkler, P. Reineker, and L. Harnau, Models and equilibrium properties of stiff molecular chains, J. Chem. Phys. 101, 8119 (1994).

Outline

Information

Sign In to Your Journals Account

Filter

Filter

Article Lookup

Enter a citation