Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making
Open accessAbstract
Cell migration during the invasion-metastasis cascade requires cancer cells to navigate a spatially complex microenvironment that presents directional choices to migrating cells. Here, we investigate cellular energetics during migration decision-making in confined spaces. Theoretical and experimental data show that energetic costs for migration through confined spaces are mediated by a balance between cell and matrix compliance as well as the degree of spatial confinement to direct decision-making. Energetic costs, driven by the cellular work needed to generate force for matrix displacement, increase with increasing cell stiffness, matrix stiffness, and degree of spatial confinement, limiting migration. By assessing energetic costs between possible migration paths, we can predict the probability of migration choice. Our findings indicate that motility in confined spaces imposes high energetic demands on migrating cells, and cells migrate in the direction of least confinement to minimize energetic costs. Therefore, therapeutically targeting metabolism may limit cancer cell migration and metastasis.
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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 [28]
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- Authors
- Zanotelli, M. R., Rahman-Zaman, A., VanderBurgh, J. A., Taufalele, P. V., Jain, A., Erickson, D., Bordeleau, F., & Reinhart-King, C. A.
- Affiliations
- Vanderbilt University (US)
- Cornell University (US)
- ORCID
- Venue
- Nature Communications
- Published
- 2019-09-13
- Volume
- 10
- Issue
- 1
- Pages
- 4185-4185
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6744572
- OpenAlex
- W2973099177
- Cited by
- 165
- References
- 73
- Citations by year
- 2026: 22 · 2025: 23 · 2024: 32 · 2023: 21 · 2022: 26 · 2021: 28 · 2020: 12 · 2012: 1
- FWCI
- 8.74
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-12-04)
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (RGPIN-2018-06214)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- tumor cell migration, metastasis, migration decisions, energetic cost, cell mechanics, cell stiffness, extracellular matrix stiffness, spatial confinement, cellular metabolism, invasion-metastasis cascade
- MeSH terms
- Adenosine Diphosphate, Adenosine Triphosphate, Biomedical Engineering, Cell Movement, Decision Making, Glucose, Humans, Microscopy, Phase-Contrast, Microscopy, Confocal, Microscopy, Atomic Force, RNA, Small Interfering, Cell Line, Tumor, Caveolin 1
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