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Long-range topotaxis as a result of supercellular topographic anisotropy during chemotaxis

J. A. J. Wondergem, M. Mytiliniou, F. C. H. de Wit, and T. G. A. Reuvers

D. Holcman*

D. Heinrich†,‡

  • *Also at DAMTP, Cambridge University, Cambridge CB3 0DDS, United Kingdom.
  • †Contact author: Doris.Heinrich@iba-heiligenstadt.de
  • ‡Also at Fraunhofer Institute for Silicate Research ISC, Würzburg, Germany; Faculty for Mathematics and Natural Sciences, Technische Universität Ilmenau, Ilmenau, Germany; Huygens-Kamerlingh Onnes Laboratory LION, Leiden University, The Netherlands.
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Phys. Rev. Research 8, 023234 – Published 1 June, 2026

DOI: https://doi.org/10.1103/pgrv-kj8x

Abstract

Highly motile cells, like patrolling leukocytes during immune response and amoeboid sarcoma cells during metastasis, navigate relatively long distances in complex environments where they encounter a wide variety of topographic structures on different length scales. Subcellular topographic substrate anisotropies have been shown to cause a drift in cell migration (topotaxis) in vitro, indicating that the topography of the extracellular environment can function as a physical guidance cue. Here, we expand on these previously reported subcellular findings by showing that supercellular asymmetries spanning long distances can also induce topotactic drift. Such long-range topotactic drift was generated by exposing highly motile cells to a subtle spatial gradient in the arrangement of cell-sized pillars. Using an analytical model and mean first-passage time analyses, we show that this type of long-range topotaxis emerges through the many interactions of persistently random migrating cells with the anisotropic confinement imposed by the gradient pillar field. We demonstrate that pillar-induced long-range topotaxis is conserved during chemotaxis, the cellular drift in response to chemical gradients. Topotactic and chemotactic drifts were found to add linearly, a finding that could have implications for in vivo studies on directed cell migration, which mostly focus on chemotactic responses alone. Moreover, as long-range topotaxis is an independent physical effect, it offers a way to steer highly motile cells independently from chemotactic guidance, which could have potential applications in cell sorting and tissue engineering.

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Phys. Rev. Research 8, 023234– Published 1 June, 2026
  • Received 5 November 2023
  • Accepted 2 April 2026
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