ArticleBiophysical journal2005
Modeling the effect of deregulated proliferation and apoptosis on the growth dynamics of epithelial cell populations in vitro.
Article in Biophysical journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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90 citing papers in PubMed, 278 citations in OpenAlex.
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- A 3D multi-agent-based model for lumen morphogenesis: the role of the biophysical properties of the extracellular matrix.Engineering with computers · 2022Article
- Morphologies of compressed active epithelial monolayers.The European physical journal. E, Soft matter · 2021Article
- How to Obtain a Mega-Intestine with Normal Morphology: In Silico Modelling of Postnatal Intestinal Growth in a Cd97-Transgenic Mouse.International journal of molecular sciences · 2021Article
- αβ/γδ T cell lineage outcome is regulated by intrathymic cell localization and environmental signals.Science advances · 2021Article
- Impact of Force Function Formulations on the Numerical Simulation of Centre-Based Models.Bulletin of mathematical biology · 2020Article
- A quantitative high-resolution computational mechanics cell model for growing and regenerating tissues.Biomechanics and modeling in mechanobiology · 2020Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We present a three-dimensional individual cell-based, biophysical model to study the effect of normal and malfunctioning growth regulation and control on the spatial-temporal organization of growing cell populations in vitro. The model includes explicit representations of typical epithelial cell growth regulation and control mechanisms, namely 1), a cell-cell contact-mediated form of growth inhibition; 2), a cell-substrate contact-dependent cell-cycle arrest; and 3), a cell-substrate contact-dependent programmed cell death (anoikis). The model cells are characterized by experimentally accessible biomechanical and cell-biological parameters. First, we study by variation of these cell-specific parameters which of them affect the macroscopic morphology and growth kinetics of a cell population within the initial expanding phase. Second, we apply selective knockouts of growth regulation and control mechanisms to investigate how the different mechanisms collectively act together. Thereby our simulation studies cover the growth behavior of epithelial cell populations ranging from undifferentiated stem cell populations via transformed variants up to tumor cell lines in vitro. We find that the cell-specific parameters, and in particular the strength of the cell-substrate anchorage, have a significant impact on the population morphology. Furthermore, they control the efficacy of the growth regulation and control mechanisms, and consequently tune the transition from controlled to uncontrolled growth that is induced by the failures of these mechanisms. Interestingly, however, we find the qualitative and quantitative growth kinetics to be remarkably robust against variations of cell-specific parameters. We compare our simulation results with experimental findings on a number of epithelial and tumor cell populations and suggest in vitro experiments to test our model predictions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.