A combined mathematical and experimental approach predicts the influence of Connexin43 on cell migration events

Claire Lorraine, Michael Watson, Scott R. Johnstone, Catherine Wright, Patricia Martin, Steven McDougall

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

In normal skin wound healing, connexin43 (Cx43) expression is reduced. However, in chronic non-healing diabetic wounds levels are significantly increased suggesting a role for Cx43 in co-ordinating wound healing and is a prime therapeutic target. Connexin mimetic peptides (CMPs) improve wound closure rates by enhancing cell migration. This occurs through alterations in either cell proliferation, cell adhesion, ECM deposition, or a combination of these.
In order to examine the roles played by each of these cellular processes, we developed a discrete off-lattice mathematical model describing individual and collective movement of cells in response to a variety of evolving environmental stimuli, including cell proliferation, chemotaxis and cell adhesion. The model suggests an early role for cell proliferation that facilitates primary migration into the wound bed. This reduces with time and distance from the wound edge. Incorporation of a chemotactic gradient released by the injured cells yield in silico data that agree with experimental time-lapse observations. Direct application of the model to in vitro conditions, where connexin expression or function is altered, are presented. The data suggests that down-regulation of Cx43 signalling at the wound edge prevents propagation of signals from injured cells that would otherwise inhibit movement into the wounded gap area. Application of CMPs that enable proliferation and migration events to be maintained, enhance wound closure rates. This versatile model has the potential to refine experimental design, inform hypotheses and predict the outcome of various therapeutic protocols where aspects of the underlying cellular behaviour remain unresolved.
Original languageEnglish
Title of host publicationProceedings of the International Gap Junction Conference
Pages125
Number of pages1
Publication statusPublished - 2013

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Keywords

  • connexin
  • mathematical modelling

Cite this

Lorraine, C., Watson, M., Johnstone, S. R., Wright, C., Martin, P., & McDougall , S. (2013). A combined mathematical and experimental approach predicts the influence of Connexin43 on cell migration events. In Proceedings of the International Gap Junction Conference (pp. 125)