Speaker
Description
Cancer invasion emerges from coupled interactions between tumour cells and the extracellular matrix (ECM), where fibre architecture, remodelling, and microenvironmental cues jointly regulate migration and growth. Building on our earlier PhysiCell framework for collagen-density-dependent spheroid invasion, we present a hybrid discrete-continuous model that incorporates fibre orientation, anisotropy, contact guidance, chemotaxis, cell-front ECM sensing, matrix displacement/degradation, and proliferation regulated by oxygen and mechanical pressure. Simulations show that invasion is enhanced when ECM fibres provide coherent directional cues: perpendicular or radial organisation promotes outward invasion, whereas parallel or tangential organisation suppresses it. Crucially, fibre anisotropy determines whether aligned architectures are effectively translated into directed motion. We further show that ECM remodelling has context-dependent effects: increasing reorientation can rescue invasion in initially restrictive matrices, but diminish invasion when the initial architecture is already favourable. The model reproduces experimentally motivated qualitative trends and yields mechanistic predictions on how tumour cells reshape and exploit ECM structure during collective invasion. These results provide a computational framework for dissecting tumour--ECM feedbacks and for designing experiments on matrix-guided invasion.
Bibliography
@ARTICLE{10.3389/fbioe.2025.1515962,
AUTHOR={Botticelli, Margherita and Metzcar, John and Phillips, Thomas and Cox, Susan and Keshavanarayana, Pradeep and Spill, Fabian },
TITLE={A hybrid computational model of cancer spheroid growth with ribose-induced collagen stiffening},
JOURNAL={Frontiers in Bioengineering and Biotechnology},
VOLUME={Volume 13 - 2025},
YEAR={2025},
URL={https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2025.1515962},
DOI={10.3389/fbioe.2025.1515962},
ISSN={2296-4185}
}
@article {Botticelli2025.09.02.673661,
author = {Botticelli, Margherita and Metzcar, John and Macklin, Paul and Keshavanarayana, Pradeep and Spill, Fabian},
title = {The role of contact guidance and ECM remodelling in cancer invasion: a computational study},
elocation-id = {2025.09.02.673661},
year = {2025},
doi = {10.1101/2025.09.02.673661},
publisher = {Cold Spring Harbor Laboratory},
URL = {https://www.biorxiv.org/content/early/2025/09/05/2025.09.02.673661},
eprint = {https://www.biorxiv.org/content/early/2025/09/05/2025.09.02.673661.full.pdf},
journal = {bioRxiv}
}
