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Organotypic Collagen I Assay: A Malleable Platform to Assess Cell Behaviour in a 3-Dimensional Context
Published on: October 13, 2011
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Cell jamming in a collagen-based interface assay is tuned by collagen density and proteolysis
Lianne Beunk1, Nan Wen1, Sjoerd van Helvert1
1Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, GA 6525, The Netherlands.
Journal of Cell Science
|November 21, 2023
Summary
Tumor cell invasion depends on tissue structure and matrix metalloproteinase (MMP) activity. Confined spaces allow invasion via cell jamming, while dense matrices require MMPs for tumor cell migration.
Area of Science:
- Biophysics
- Cancer Biology
- Biomaterials
Background:
- Tumor cell invasion involves matrix metalloproteinase (MMP)-mediated remodeling and adaptation to tissue geometry.
- Previous 3D models explored porous or aligned architectures, but the role of architecture in MMP-dependent invasion remains unclear.
Purpose of the Study:
- To investigate tumor cell invasion efficacy, mode, and MMP dependence across different tissue architectures.
- To compare invasion into confining clefts versus dense porous matrices.
Main Methods:
- Development of a 3D interface assay with a cleft between collagen lattices.
- In silico modeling to predict cell migration behavior.
- Experimental verification using MMP inhibition and collagen degradation assessment.
Main Results:
- In silico models predicted MMP-independent migration in clefts and MMP-dependent migration in dense matrices.
- Experimental results confirmed that collagen degradation inhibition compromised migration in 3D collagen but not in interface-guided migration (cell jamming).
Conclusions:
- Tissue architecture significantly influences tumor cell invasion strategies and MMP dependence.
- The 3D interface assay provides a model for studying invasion in relevant interstitial tissue topologies.
- Findings may inform molecular interventions targeting tumor invasion.
