The phenotype of cancer cell invasion controlled by fibril diameter and pore size of 3D collagen networks
Open accessAbstract
The behavior of cancer cells is strongly influenced by the properties of extracellular microenvironments, including topology, mechanics and composition. As topological and mechanical properties of the extracellular matrix are hard to access and control for in-depth studies of underlying mechanisms in vivo, defined biomimetic in vitro models are needed. Herein we show, how pore size and fibril diameter of collagen I networks distinctively regulate cancer cell morphology and invasion. Three-dimensional collagen I matrices with a tight control of pore size, fibril diameter and stiffness were reconstituted by adjustment of concentration and pH value during matrix reconstitution. At first, a detailed analysis of topology and mechanics of matrices using confocal laser scanning microscopy, image analysis tools and force spectroscopy indicate pore size and not fibril diameter as the major determinant of matrix elasticity. Secondly, by using two different breast cancer cell lines (MDA-MB-231 and MCF-7), we demonstrate collagen fibril diameter--and not pore size--to primarily regulate cell morphology, cluster formation and invasion. Invasiveness increased and clustering decreased with increasing fibril diameter for both, the highly invasive MDA-MB-231 cells with mesenchymal migratory phenotype and the MCF-7 cells with amoeboid migratory phenotype. As this behavior was independent of overall pore size, matrix elasticity is shown to be not the major determinant of the cell characteristics. Our work emphasizes the complex relationship between structural-mechanical properties of the extracellular matrix and invasive behavior of cancer cells. It suggests a correlation of migratory and invasive phenotype of cancer cells in dependence on topological and mechanical features of the length scale of single fibrils and not on coarse-grained network properties.
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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 [27]
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- Authors
- Sapudom, J., Rubner, S., Martin, S., Kurth, T., Riedel, S., Mierke, C. T., & Pompe, T.
- Affiliations
- Leipzig University (DE)
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 52
- Pages
- 367-375
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2086310075
- Cited by
- 195
- References
- 51
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 16 · 2023: 20 · 2022: 18 · 2021: 26 · 2020: 34 · 2019: 8 · 2018: 16 · 2017: 19 · 2016: 12 · 2015: 3
- FWCI
- 8.87
- Type
- journal article
- Language
- en
- Open access
- green
- ul.qucosa.de
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Qucosa (Saxon State and University Library Dresden) (submittedVersion, other-oa)
- Funders
- 'European Social Funds' and Free State of Saxony (SAB 100147954, SAB 100148830)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- tumor invasion, pore size, extracellular matrix mechanics, matrix elasticity, cell morphology, cell clustering, breast cancer, MDA-MB-231 cells, MCF-7 cells, mesenchymal migration, amoeboid migration
- MeSH terms
- Cell Movement, Colloids, Elasticity, Extracellular Matrix, Humans, Hydrogen-Ion Concentration, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Phenotype, Stress, Mechanical, Microscopy, Confocal, Cell Culture Techniques, Collagen Type I, Biomimetics, Cell Line, Tumor, MCF-7 Cells
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