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Title: Exploring hypotheses of the actions of TGF-β1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis
Authors: Sun, Tao
Adra, Salem
Smallwood, Rod
Holcombe, Mike
MacNeil, Sheila
Issue Date: 2009
Publisher: Public Library of Science (© 2009 Sun et al.)
Citation: SUN, T. ... et al, 2009. Exploring hypotheses of the actions of TGF-β1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis. PLoS ONE, 4 (12), e8515
Abstract: In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-β1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-β1 literature–derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units (keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-β1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged (by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-β1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-β1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing.
Description: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Version: Published
DOI: 10.1371/journal.pone.0008515
URI: https://dspace.lboro.ac.uk/2134/24954
Publisher Link: http://dx.doi.org/10.1371/journal.pone.0008515
Appears in Collections:Published Articles (Chemical Engineering)

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