Book ChapterDOI
An in silico analogue of in vitro systems used to study epithelial cell morphogenesis
Mark R. Grant,C. Anthony Hunt +1 more
- pp 285-297
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TLDR
A low-resolution system analogue in which space, events, and time are discretized; object interaction uses a two-dimensional grid similar to a cellular automaton to facilitate experimental exploration of outcomes from changing components and features.Abstract:
In vitro model systems are used to study epithelial cell growth, morphogenesis, differentiation, and transition to cancer-like forms. MDCK cell lines (from immortalized kidney epithelial cells) are widely used examples. Prominent in vitro phenotypic attributes include stable cyst formation in embedded culture, inverted cyst formation in suspension culture, and lumen formation in overlay culture. We present a low-resolution system analogue in which space, events, and time are discretized; object interaction uses a two-dimensional grid similar to a cellular automaton. The framework enables “cell” agents to act independent using an embedded logic based on axioms. In silico growth and morphology can mimic in vitro observations in four different simulated environments. Matched behaviors include stable “cyst” formation. The in silico system is designed to facilitate experimental exploration of outcomes from changing components and features, including the embedded logic (the in silico analogue of a mutation or epigenetic change). Some simulated behaviors are sensitive to changes in logic. In two cases, the change caused cancer-like growth patterns to emerge.read more
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Journal ArticleDOI
At the Biological Modeling and Simulation Frontier
C. Anthony Hunt,C. Anthony Hunt,Glen E. P. Ropella,Tai Ning Lam,Jonathan Tang,Sean H. J. Kim,Jesse A. Engelberg,Shahab Sheikh-Bahaei +7 more
TL;DR: It is argued that the familiar inductive approaches contribute to the general inefficiencies being experienced by pharmaceutical R&D, and that use of synthetic approaches accelerates and improves R &D decision-making and thus the drug development process.
References
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TL;DR: The existence of patterns of mechanical forces that originate from the contraction of cells, emerge from their multicellular organization, and result in patterns of growth are demonstrated, demonstrating that tissue form itself can feed back to regulate patterns of proliferation.
Journal ArticleDOI
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TL;DR: A number of biologically motivated cellular automata that arise in models of excitable and oscillatory media, in developmental biology, in neurobiology, and in population biology are reviewed.
Journal ArticleDOI
Building epithelial architecture: insights from three-dimensional culture models
TL;DR: It is proposed that the morphogenetic behaviour of epithelial cells is guided by two distinct elements: an intrinsic differentiation programme that drives formation of a lumen-enclosing monolayer, and a growth factor-induced, transient de-differentiation that allows this monolayers to be remodelled.