Physical limits of cell migration: control by ECM space and nuclear deformation and tuning by proteolysis and traction force
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Cell migration through 3D tissue depends on a physicochemical balance between cell deformability and physical tissue constraints. Migration rates are further governed by the capacity to degrade ECM by proteolytic enzymes, particularly matrix metalloproteinases (MMPs), and integrin- and actomyosin-mediated mechanocoupling. Yet, how these parameters cooperate when space is confined remains unclear. Using MMP-degradable collagen lattices or nondegradable substrates of varying porosity, we quantitatively identify the limits of cell migration by physical arrest. MMP-independent migration declined as linear function of pore size and with deformation of the nucleus, with arrest reached at 10% of the nuclear cross section (tumor cells, 7 µm²; T cells, 4 µm²; neutrophils, 2 µm²). Residual migration under space restriction strongly depended upon MMP-dependent ECM cleavage by enlarging matrix pore diameters, and integrin- and actomyosin-dependent force generation, which jointly propelled the nucleus. The limits of interstitial cell migration thus depend upon scaffold porosity and deformation of the nucleus, with pericellular collagenolysis and mechanocoupling as modulators.
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Collagen type I-based hydrogels enable tunable mechanical and structural properties, in particular stiffness (0.01-1 kPa) and porosity (0.2-15 μm pore diameters), by changes in concentration, polymerization conditions, or glycation.
“Collagen type I-based hydrogels enable tunable mechanical and structural properties, in particular stiffness (0.01-1 kPa) and porosity (0.2-15 μm pore diameters), by changes in concentration, polymerization conditions (such as pH or temperature changes), or glycation [26][27][28].”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [26]
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Ghazanfari, D., Ren, L., Cantú, M. S., & King, M. R. (2025) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2025.100619 · Cited by 3 · see citing works
- Authors
- Wolf, K., te Lindert, M., Krause, M., Alexander, S., te Riet, J., Willis, A. L., Hoffman, R. M., Figdor, C. G., Weiss, S. J., & Friedl, P.
- Affiliations
- Radboud University Medical Center (NL)
- Department of Cell Biology 1 and 2
- The University of Texas MD Anderson Cancer Center (US)
- University of Michigan (US)
- University of California San Diego (US)
- Corresponding author
- Wolf, Katarina
- Friedl, Peter
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2013-06-24
- Volume
- 201
- Issue
- 7
- Pages
- 1069-1084
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC3691458
- OpenAlex
- W2110344693
- Cited by
- 1,375
- References
- 75
- Citations by year
- 2026: 79 · 2025: 100 · 2024: 94 · 2023: 112 · 2022: 108 · 2021: 123 · 2020: 141 · 2019: 120 · 2018: 131 · 2017: 99 · 2016: 107 · 2015: 78 · 2014: 67 · 2013: 14 · 2012: 1
- FWCI
- 51.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (680-47-421, 917.10.364, 918.11.626)
- National Cancer Institute (R01CA088308, R01 CA71699, R01CA071699, R01 CA88308)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK020572)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- cell migration, extracellular matrix, matrix metalloproteinases, collagen degradation, nuclear deformation, pore size, scaffold porosity, integrins, actomyosin, traction force, interstitial migration, cancer cells, T cells, neutrophils
- MeSH terms
- Animals, Cattle, Cell Line, Cell Movement, Collagen, Extracellular Matrix, Humans, Kinetics, Surface Properties, Integrins, Hydrogels, Matrix Metalloproteinases, Rats, Proteolysis
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