A hybrid computational model of cancer spheroid growth with ribose-induced collagen stiffening DOI Creative Commons

Margherita Botticelli,

John Metzcar,

Thomas Phillips

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: April 9, 2025

Metastasis, the leading cause of death in cancer patients, arises when cells disseminate from a primary solid tumour to distant organs. Growth and invasion often involve collective cell migration, which is profoundly influenced by cell-cell interactions extracellular matrix (ECM). The ECM's biochemical composition mechanical properties, such as stiffness, regulate behaviour migration dynamics. Mathematical modelling serves pivotal tool for studying predicting these complex dynamics, with hybrid discrete-continuous models offering powerful approach combining agent-based representations continuum descriptions surrounding microenvironment. In this study, we investigate impact ECM modulated via ribose-induced collagen cross-linking, on spheroid growth invasion. We employed model implemented PhysiCell simulate successfully replicating three-dimensional vitro experiments. incorporates detailed cell-ECM interactions, remodelling, proliferation. Our simulations align experimental observations two breast lines, non-invasive MCF7 invasive HCC 1954, under varying stiffness conditions. results demonstrate that increased due cross-linking inhibits cells, whereas remain largely unaffected. Furthermore, our show higher degradation not only enables but also facilitates formation multicellular protrusions. Conversely, increasing maximum speed can reach enhances while promoting single-cell This understanding interplay between proliferation, paving way future studies incorporating additional characteristics microenvironmental

Language: Английский

A hybrid computational model of cancer spheroid growth with ribose-induced collagen stiffening DOI Creative Commons

Margherita Botticelli,

John Metzcar,

Thomas Phillips

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: April 9, 2025

Metastasis, the leading cause of death in cancer patients, arises when cells disseminate from a primary solid tumour to distant organs. Growth and invasion often involve collective cell migration, which is profoundly influenced by cell-cell interactions extracellular matrix (ECM). The ECM's biochemical composition mechanical properties, such as stiffness, regulate behaviour migration dynamics. Mathematical modelling serves pivotal tool for studying predicting these complex dynamics, with hybrid discrete-continuous models offering powerful approach combining agent-based representations continuum descriptions surrounding microenvironment. In this study, we investigate impact ECM modulated via ribose-induced collagen cross-linking, on spheroid growth invasion. We employed model implemented PhysiCell simulate successfully replicating three-dimensional vitro experiments. incorporates detailed cell-ECM interactions, remodelling, proliferation. Our simulations align experimental observations two breast lines, non-invasive MCF7 invasive HCC 1954, under varying stiffness conditions. results demonstrate that increased due cross-linking inhibits cells, whereas remain largely unaffected. Furthermore, our show higher degradation not only enables but also facilitates formation multicellular protrusions. Conversely, increasing maximum speed can reach enhances while promoting single-cell This understanding interplay between proliferation, paving way future studies incorporating additional characteristics microenvironmental

Language: Английский

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