ArticleTheoretical biology & medical modelling2009
Computational investigation of epithelial cell dynamic phenotype in vitro.
Article in Theoretical biology & medical modelling, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Predicting organoid morphology through a phase field model: Insights into cell division and lumenal pressure.PLoS computational biology · 2025Article
- Cell-extracellular matrix interactions in the fluidic phase direct the topology and polarity of self-organized epithelial structures.Cell proliferation · 2021Article
- The two faces of titanium dioxide nanoparticles bio-camouflage in 3D bone spheroids.Scientific reports · 2019Article
- Relational grounding facilitates development of scientifically useful multiscale models.Theoretical biology & medical modelling · 2011Review
- MDCK cystogenesis driven by cell stabilization within computational analogues.PLoS computational biology · 2011Article
- Molecular regulation of lumen morphogenesis.Current biology : CB · 2011Review
- STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis.Molecular biology of the cell · 2010Article
- Integrative multicellular biological modeling: a case study of 3D epidermal development using GPU algorithms.BMC systems biology · 2010Article
- A computational approach to resolve cell level contributions to early glandular epithelial cancer progression.BMC systems biology · 2009Article
- At the biological modeling and simulation frontier.Pharmaceutical research · 2009Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
backgroundWhen grown in three-dimensional (3D) cultures, epithelial cells typically form cystic organoids that recapitulate cardinal features of in vivo epithelial structures. Characterizing essential cell actions and their roles, which constitute the system's dynamic phenotype, is critical to gaining deeper insight into the cystogenesis phenomena.
methodsStarting with an earlier in silico epithelial analogue (ISEA1) that validated for several Madin-Darby canine kidney (MDCK) epithelial cell culture attributes, we built a revised analogue (ISEA2) to increase overlap between analogue and cell culture traits. Both analogues used agent-based, discrete event methods. A set of axioms determined ISEA behaviors; together, they specified the analogue's operating principles. A new experimentation framework enabled tracking relative axiom use and roles during simulated cystogenesis along with establishment of the consequences of their disruption.
resultsISEA2 consistently produced convex cystic structures in a simulated embedded culture. Axiom use measures provided detailed descriptions of the analogue's dynamic phenotype. Dysregulating key cell death and division axioms led to disorganized structures. Adhering to either axiom less than 80% of the time caused ISEA1 to form easily identified morphological changes. ISEA2 was more robust to identical dysregulation. Both dysregulated analogues exhibited characteristics that resembled those associated with an in vitro model of early glandular epithelial cancer.
conclusionWe documented the causal chains of events, and their relative roles, responsible for simulated cystogenesis. The results stand as an early hypothesis--a theory--of how individual MDCK cell actions give rise to consistently roundish, cystic organoids.
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