Single-cell migration along and against confined haptotactic gradients

article Single-cell migration along and against confined haptotactic gradients published yes Isabela Corina Fortunato author David Brückner author e1e86031-6537-11eb-953a-f7ab92be508d0000-0001-7205-2975 Steffen Grosser author Rohit Nautiyal author Leone Rossetti author Miquel Bosch-Padrós author Jonel Trebicka author Pere Roca-Cusachs author Raimon Sunyer author Edouard B Hannezo author 3A9DB764-F248-11E8-B48F-1D18A9856A870000-0001-6005-1561 Xavier Trepat author EdHa department A mechano-chemical theory for stem cell fate decisions in organoid development project Haptotaxis is the process of directed cell migration along gradients of extracellular matrix density and is central to morphogenesis, immune responses and cancer invasion. It is commonly assumed that cells respond to these gradients by migrating directionally towards the regions of highest ligand density. In contrast with this view, here we show that cells exposed to micropatterned fibronectin gradients exhibit a wide range of complex trajectories, including directed haptotactic migration up the gradient but also linear oscillations and circles with extended periods of migration down the gradient. To explain this behaviour, we developed a biophysical model of haptotactic cell migration based on a coarse-grained molecular clutch model coupled to persistent stochastic polarity dynamics. Although initial haptotactic migration is explained by the differential friction at the front and back of the cell, the observed complex trajectories over longer timescales arise from the interplay between differential friction, persistence and physical confinement. Overall, our study reveals that confinement and persistence modulate the ability of cells to sense and respond to haptotactic cues and provides a framework for understanding how cells navigate complex environments. Springer Nature2025 eng Nature Physics 1745-2473 1745-2481 00158165990000110.1038/s41567-025-03015-3 211638-1647 Fortunato, I. C., Brückner, D., Grosser, S., Nautiyal, R., Rossetti, L., Bosch-Padrós, M., … Trepat, X. (2025). Single-cell migration along and against confined haptotactic gradients. Nature Physics. Springer Nature. <a href="https://doi.org/10.1038/s41567-025-03015-3">https://doi.org/10.1038/s41567-025-03015-3</a> Fortunato, Isabela Corina, et al. “Single-Cell Migration along and against Confined Haptotactic Gradients.” Nature Physics, vol. 21, Springer Nature, 2025, pp. 1638–47, doi:<a href="https://doi.org/10.1038/s41567-025-03015-3">10.1038/s41567-025-03015-3</a>. Fortunato IC, Brückner D, Grosser S, Nautiyal R, Rossetti L, Bosch-Padrós M, Trebicka J, Roca-Cusachs P, Sunyer R, Hannezo EB, Trepat X. 2025. Single-cell migration along and against confined haptotactic gradients. Nature Physics. 21, 1638–1647. Fortunato, Isabela Corina, David Brückner, Steffen Grosser, Rohit Nautiyal, Leone Rossetti, Miquel Bosch-Padrós, Jonel Trebicka, et al. “Single-Cell Migration along and against Confined Haptotactic Gradients.” Nature Physics. Springer Nature, 2025. <a href="https://doi.org/10.1038/s41567-025-03015-3">https://doi.org/10.1038/s41567-025-03015-3</a>. Fortunato IC, Brückner D, Grosser S, et al. Single-cell migration along and against confined haptotactic gradients. Nature Physics. 2025;21:1638-1647. doi:<a href="https://doi.org/10.1038/s41567-025-03015-3">10.1038/s41567-025-03015-3</a> I. C. Fortunato et al., “Single-cell migration along and against confined haptotactic gradients,” Nature Physics, vol. 21. Springer Nature, pp. 1638–1647, 2025. I.C. Fortunato, D. Brückner, S. Grosser, R. Nautiyal, L. Rossetti, M. Bosch-Padrós, J. Trebicka, P. Roca-Cusachs, R. Sunyer, E.B. Hannezo, X. Trepat, Nature Physics 21 (2025) 1638–1647. 204312025-10-05T22:01:36Z2026-01-05T14:26:28Z