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Falsifying computational models of endothelial cell network formation through quantitative comparison with in vitro
Tessa M Vergroesen1, Vincent Vermeulen1, Roeland M H Merks1,2
1Institute of Biology Leiden, Leiden University, Leiden, The Netherlands.
Plos Computational Biology
|April 30, 2025
Summary
Computational models of angiogenesis can reproduce experimental results using different assumptions, making validation difficult. This study validates models by comparing dynamic experimental data with computational predictions, finding the cell elongation model best fits experimental data.
Area of Science:
- Cell biology
- Biophysics
- Computational biology
Background:
- Angiogenesis involves endothelial cell migration, proliferation, and network formation.
- Computational models aid in understanding if current knowledge explains endothelial cell network formation.
- Validating these models is challenging due to different assumptions yielding similar outcomes.
Purpose of the Study:
- To validate computational models of endothelial cell network formation against experimental data.
- To compare the dynamical characteristics of in vitro angiogenesis with three distinct mathematical models.
- To assess model performance under varying cell densities.
Main Methods:
- Dynamical analysis of time-lapse in vitro endothelial cell network formation experiments.
- Comparison of experimental data with three computational models: cell elongation, contact-inhibited chemotaxis, and mechanical cell-cell communication.
- Utilized a custom ImageJ pipeline for video analysis and tested model responses to cell density changes.
Main Results:
- The cell elongation model best captured the remodeling phase of in vitro endothelial cell network formation.
- In vitro, final lacunae size and number were independent of initial cell density.
- This density independence was reproduced by the cell elongation model but not by the other two models.
Conclusions:
- The cell elongation model provides a more accurate representation of in vitro angiogenesis remodeling.
- Model validation requires comparing time-resolved data and experimental condition variations.
- This approach aids in distinguishing between computational models of angiogenesis.
