Anisotropic forces from spatially constrained focal adhesions mediate contact guidance directed cell migration
Open accessAbstract
Directed migration by contact guidance is a poorly understood yet vital phenomenon, particularly for carcinoma cell invasion on aligned collagen fibres. We demonstrate that for single cells, aligned architectures providing contact guidance cues induce constrained focal adhesion maturation and associated F-actin alignment, consequently orchestrating anisotropic traction stresses that drive cell orientation and directional migration. Consistent with this understanding, relaxing spatial constraints to adhesion maturation either through reduction in substrate alignment density or reduction in adhesion size diminishes the contact guidance response. While such interactions allow single mesenchymal-like cells to spontaneously 'sense' and follow topographic alignment, intercellular interactions within epithelial clusters temper anisotropic cell-substratum forces, resulting in substantially lower directional response. Overall, these results point to the control of contact guidance by a balance of cell-substratum and cell-cell interactions, modulated by cell phenotype-specific cytoskeletal arrangements. Thus, our findings elucidate how phenotypically diverse cells perceive ECM alignment at the molecular level.
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ECM anisotropy is a hallmark in many cancers.
“Because ECM anisotropy is a hallmark in many cancers”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [22]
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- Authors
- Ray, A., Lee, O., Win, Z., Edwards, R. M., Alford, P. W., Kim, D.-H., & Provenzano, P. P.
- Affiliations
- University of Minnesota (US)
- University of Washington (US)
- Corresponding author
- Provenzano, Paolo P.
- Venue
- Nature Communications
- Published
- 2017-04-12
- Volume
- 8
- Issue
- 1
- Pages
- 14923-14923
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5394287
- OpenAlex
- W2607472835
- Cited by
- 293
- References
- 70
- Citations by year
- 2026: 21 · 2025: 30 · 2024: 24 · 2023: 35 · 2022: 29 · 2021: 39 · 2020: 38 · 2019: 41 · 2018: 29 · 2017: 5
- FWCI
- 16.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Science Foundation (1553255)
- American Cancer Society (RSG‐14‐171‐01‐CSM)
- University of Minnesota
- National Institutes of Health
- College of Science and Engineering, University of Minnesota
- Masonic Cancer Center, University of Minnesota
- National Cancer Institute (R01CA181385, U54CA210190)
- National Institute of Biomedical Imaging and Bioengineering (R03EB016969)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- contact guidance, directed cell migration, focal adhesions, collagen fiber alignment, cell-substrate interaction, cell-cell interactions, mesenchymal cells, extracellular matrix alignment, cell orientation
- MeSH terms
- Actins, Animals, Cell Adhesion, Cell Communication, Cell Movement, Humans, Actin Cytoskeleton, Neoplasms, Anisotropy, Microscopy, Confocal, Focal Adhesions, Cell Line, Tumor, Mice, Time-Lapse Imaging
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