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Agent-based computational modeling of wounded epithelial cell monolayers

Walker, D.C., Hill, G., Wood, S.M., Smallwood, R.H. and Southgate, J. (2004) Agent-based computational modeling of wounded epithelial cell monolayers. IEEE Transactions on Nanobioscience, 3 (3). pp. 153-163. ISSN 1536-1241


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Computational modeling of biological systems, or ‘in silico biology’ is an emerging tool for understanding structure and order in biological tissues. Computational models of the behavior of epithelial cells in monolayer cell culture have been developed and used to predict the healing characteristics of scratch wounds made to urothelial cell cultures maintained in low and physiological [Ca2+] environments. Both computational models and in vitro experiments demonstrated that in low exogenous [Ca2+], the closure of 500mm scratch wounds was achieved primarily by cell migration into the denuded area. The wound healing rate in low (0.09mM) [Ca2+] was approximately twice as rapid as in physiological (2mM) [Ca2+]. Computational modeling predicted that in cell cultures that are actively proliferating, no increase in the fraction of cells in S-phase would be expected, and this conclusion was supported experimentally in vitro by BrdU incorporation assay. We have demonstrated that a simple rule-based model of cell behavior, incorporating rules relating to contact inhibition of proliferation and migration, is sufficient to qualitatively predict the calcium-dependent pattern of wound closure observed in vitro. Differences between the in vitro and in silico models suggest a role for wound-induced signaling events in urothelial cell cultures.

Item Type: Article
Copyright, Publisher and Additional Information: © 2004 IEEE. Personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution to servers or lists, or to reuse any copyrighted component of this work in other works must be obtained from the IEEE. Additional information at http://www.dcs.shef.ac.uk/~rod/Integrative_Biology.html
Keywords: Calcium, Computational modeling, emergent structure, urinary epithelium, wound healing
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Computer Science (Sheffield)
Depositing User: Rod Smallwood
Date Deposited: 28 Apr 2005
Last Modified: 04 Jun 2014 13:24
Published Version: http://www.ieee.org/portal/site/mainsite/menuitem....
Status: Published
Refereed: Yes
Identification Number: 10.1109/TNB.2004.833680
URI: http://eprints.whiterose.ac.uk/id/eprint/422

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