---
OA_place: repository
OA_type: green
_id: '20431'
abstract:
- lang: eng
  text: 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.
acknowledgement: We thank all the members of our groups for discussions and support.
  We thank A. Menéndez, S. Usieto, M. Purciolas and E. Coderch for technical assistance.
  We thank G. Charras (London Centre for Nanotechnology, UK) and M. Sheetz (Columbia
  University, USA) for sharing cells used in this work. We thank J. Ivaska (University
  of Turku, Finland) for sharing integrin α5-GFP DNA plasmid. We thank P. Guillamat
  for technical advice and A. Labernardie for providing the microfluidic channels.
  We thank M. Gómez-González for sharing the 2D traction microscopy algorithm. Finally,
  we thank P. Guillamat, J. Abenza, G. Ceada, L. Faure, E. Dalaka, M. Matejčić, A.
  Beedle, I. Granero, O. Baguer, A. Albajar and N. Chahare for discussions. This paper
  was funded by the Generalitat de Catalunya (Grant Nos. AGAUR SGR-2017-01602 to X.T.
  and 2021 SGR 00523 to R.S. and the CERCA Programme and ICREA Academia awards to
  P.R.-C.), the Spanish Ministry for Science and Innovation MICCINN/FEDER (Grant Nos.
  PID2021-128635NB-I00, MCIN/AEI/10.13039/501100011033 and ERDF-EU A way of making
  Europe to X.T., PID2021-128674OB-I00 and CNS2022-135533 to R.S. and PID2019-110298GB-I00
  to P.R.-C.), the European Research Council (Grant Nos. 101097753 to P.R.-C. and
  Adv-883739 to X.T.), Fundació la Marató de TV3 (Project Award 201903-30-31-32 to
  X.T.), the European Commission (Grant No. H2020-FETPROACT-01-2016-731957 to P.R.-C.
  and X.T.) and La Caixa Foundation (Grant No. LCF/PR/HR20/52400004 to P.R.-C. and
  X.T.). R.S. is a Serra-Hunter fellow. D.B.B. was supported by the NOMIS foundation
  as a NOMIS fellow, by the European Molecular Biology Organization (Postdoctoral
  Fellowship ALTF 343-2022) and by the Austrian Academy of Sciences through an APART-MINT
  Fellowship. I.C.F. acknowledges support from the European Foundation for the Study
  of Chronic Liver Failure. IBEC is recipient of a Severo Ochoa Award of Excellence
  from MINECO.
article_processing_charge: No
article_type: original
author:
- first_name: Isabela Corina
  full_name: Fortunato, Isabela Corina
  last_name: Fortunato
- first_name: David
  full_name: Brückner, David
  id: e1e86031-6537-11eb-953a-f7ab92be508d
  last_name: Brückner
  orcid: 0000-0001-7205-2975
- first_name: Steffen
  full_name: Grosser, Steffen
  last_name: Grosser
- first_name: Rohit
  full_name: Nautiyal, Rohit
  last_name: Nautiyal
- first_name: Leone
  full_name: Rossetti, Leone
  last_name: Rossetti
- first_name: Miquel
  full_name: Bosch-Padrós, Miquel
  last_name: Bosch-Padrós
- first_name: Jonel
  full_name: Trebicka, Jonel
  last_name: Trebicka
- first_name: Pere
  full_name: Roca-Cusachs, Pere
  last_name: Roca-Cusachs
- first_name: Raimon
  full_name: Sunyer, Raimon
  last_name: Sunyer
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Xavier
  full_name: Trepat, Xavier
  last_name: Trepat
citation:
  ama: Fortunato IC, Brückner D, Grosser S, et al. Single-cell migration along and
    against confined haptotactic gradients. <i>Nature Physics</i>. 2025;21:1638-1647.
    doi:<a href="https://doi.org/10.1038/s41567-025-03015-3">10.1038/s41567-025-03015-3</a>
  apa: 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. <i>Nature Physics</i>. Springer Nature. <a href="https://doi.org/10.1038/s41567-025-03015-3">https://doi.org/10.1038/s41567-025-03015-3</a>
  chicago: 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.” <i>Nature Physics</i>. Springer
    Nature, 2025. <a href="https://doi.org/10.1038/s41567-025-03015-3">https://doi.org/10.1038/s41567-025-03015-3</a>.
  ieee: I. C. Fortunato <i>et al.</i>, “Single-cell migration along and against confined
    haptotactic gradients,” <i>Nature Physics</i>, vol. 21. Springer Nature, pp. 1638–1647,
    2025.
  ista: 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.
  mla: Fortunato, Isabela Corina, et al. “Single-Cell Migration along and against
    Confined Haptotactic Gradients.” <i>Nature Physics</i>, 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>.
  short: 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.
corr_author: '1'
date_created: 2025-10-05T22:01:36Z
date_published: 2025-10-01T00:00:00Z
date_updated: 2026-01-05T14:26:28Z
day: '01'
department:
- _id: EdHa
doi: 10.1038/s41567-025-03015-3
external_id:
  isi:
  - '001581659900001'
intvolume: '        21'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2024.12.02.626413
month: '10'
oa: 1
oa_version: Preprint
page: 1638-1647
project:
- _id: 34e2a5b5-11ca-11ed-8bc3-b2265616ef0b
  grant_number: ALTF 343-2022
  name: A mechano-chemical theory for stem cell fate decisions in organoid development
publication: Nature Physics
publication_identifier:
  eissn:
  - 1745-2481
  issn:
  - 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Single-cell migration along and against confined haptotactic gradients
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 21
year: '2025'
...