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An integrated systems biology approach to understanding the rules of keratinocyte colony formation
journal contribution
posted on 2017-05-12, 12:00 authored by Tao SunTao Sun, Phil McMinn, Simon Coakley, Mike Holcombe, Rod Smallwood, Sheila MacNeilClosely coupled in vitro and in virtuo models have been used to explore the self-organization of normal human keratinocytes (NHK). Although it can be observed experimentally, we lack the tools to explore many biological rules that govern NHK self-organization. An agent-based computational model was developed, based on rules derived from literature, which predicts the dynamic multicellular morphogenesis of NHK and of a keratinocyte cell line (HaCat cells) under varying extracellular Ca++ concentrations. The model enables in virtuo exploration of the relative importance of biological rules and was used to test hypotheses in virtuo which were subsequently examined in vitro. Results indicated that cell–cell and cell–substrate adhesions were critically important to NHK self-organization. In contrast, cell cycle length and the number of divisions that transit-amplifying cells could undergo proved non-critical to the final organization. Two further hypotheses, to explain the growth behaviour of HaCat cells, were explored in virtuo—an inability to differentiate and a differing sensitivity to extracellular calcium. In vitro experimentation provided some support for both hypotheses. For NHKs, the prediction was made that the position of stem cells would influence the pattern of cell migration post-wounding. This was then confirmed experimentally using a scratch wound model.
History
School
- Aeronautical, Automotive, Chemical and Materials Engineering
Department
- Chemical Engineering
Published in
Journal of The Royal Society InterfaceVolume
4Issue
17Pages
1077 - 1092Citation
SUN, T. ... et al, 2007. An integrated systems biology approach to understanding the rules of keratinocyte colony formation. Journal of The Royal Society Interface, 4 (17), pp.1077-1092Publisher
© The Royal SocietyVersion
- AM (Accepted Manuscript)
Publisher statement
This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/Publication date
2007Notes
This paper is closed access.ISSN
1742-5689eISSN
1742-5662Publisher version
Language
- en