dorsal/arxiv
View SchemaAb initio phenomenological simulation of the growth of large tumor cell populations
| Authors | Roberto Chignola, Alessio Del Fabbro, Chiara Dalla Pellegrina, Edoardo Milotti |
|---|---|
| Categories | |
| ArXiv ID | physics/0703007 |
| URL | https://arxiv.org/abs/physics/0703007 |
| DOI | 10.1088/1478-3975/4/2/005 |
Abstract
In a previous paper we have introduced a phenomenological model of cell metabolism and of the cell cycle to simulate the behavior of large tumor cell populations (Chignola R and Milotti E, Phys. Biol. 2 (2005) 8-22). Here we describe a refined and extended version of the model that includes some of the complex interactions between cells and their surrounding environment. The present version takes into consideration several additional energy-consuming biochemical pathways such as protein and DNA synthesis, the tuning of extracellular pH and of the cell membrane potential. The control of the cell cycle - that was previously modeled by means of ad hoc thresholds - has been directly addressed here by considering checkpoints from proteins that act as targets for phosphorylation on multiple sites. As simulated cells grow, they can now modify the chemical composition of the surrounding environment which in turn acts as a feedback mechanism to tune cell metabolism and hence cell proliferation: in this way we obtain growth curves that match quite well those observed in vitro with human leukemia cell lines. The model is strongly constrained and returns results that can be directly compared with actual experiments, because it uses parameter values in narrow ranges estimated from experimental data, and in perspective we hope to utilize it to develop in silico studies of the growth of very large tumor cell populations (10^6 cells or more) and to support experimental research. In particular, the program is used here to make predictions on the behaviour of cells grown in a glucose-poor medium: these predictions are confirmed by experimental observation.
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"abstract": "In a previous paper we have introduced a phenomenological model of cell\nmetabolism and of the cell cycle to simulate the behavior of large tumor cell\npopulations (Chignola R and Milotti E, Phys. Biol. 2 (2005) 8-22). Here we\ndescribe a refined and extended version of the model that includes some of the\ncomplex interactions between cells and their surrounding environment. The\npresent version takes into consideration several additional energy-consuming\nbiochemical pathways such as protein and DNA synthesis, the tuning of\nextracellular pH and of the cell membrane potential. The control of the cell\ncycle - that was previously modeled by means of ad hoc thresholds - has been\ndirectly addressed here by considering checkpoints from proteins that act as\ntargets for phosphorylation on multiple sites. As simulated cells grow, they\ncan now modify the chemical composition of the surrounding environment which in\nturn acts as a feedback mechanism to tune cell metabolism and hence cell\nproliferation: in this way we obtain growth curves that match quite well those\nobserved in vitro with human leukemia cell lines. The model is strongly\nconstrained and returns results that can be directly compared with actual\nexperiments, because it uses parameter values in narrow ranges estimated from\nexperimental data, and in perspective we hope to utilize it to develop in\nsilico studies of the growth of very large tumor cell populations (10^6 cells\nor more) and to support experimental research. In particular, the program is\nused here to make predictions on the behaviour of cells grown in a glucose-poor\nmedium: these predictions are confirmed by experimental observation.",
"arxiv_id": "physics/0703007",
"authors": [
"Roberto Chignola",
"Alessio Del Fabbro",
"Chiara Dalla Pellegrina",
"Edoardo Milotti"
],
"categories": [
"physics.bio-ph",
"q-bio.CB"
],
"doi": "10.1088/1478-3975/4/2/005",
"title": "Ab initio phenomenological simulation of the growth of large tumor cell populations",
"url": "https://arxiv.org/abs/physics/0703007"
},
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