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Cell population-based model of dermal wound invasion with heterogeneous intracellular signaling properties

Michael I. Monine and Jason M. Haugh
Volume 2, Issue 2
April/May/June 2008
Pages 137 - 146

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A deterministic model of dermal wound invasion, which accounts for the platelet-derived growth factor (PDGF) gradient sensing mechanism in fibroblasts mediated by cell surface receptors and the phosphoinositide 3-kinase (PI3K) signal transduction pathway, was previously described (Biophys J 2006; 90:2297-2308). Here, we extend that work and implement a hybrid modeling strategy that treats fibroblasts as discrete entities endowed with heterogeneous properties, namely receptor, PI3K and 3’ phosphoinositide phosphatase expression levels. Analysis of the model suggests that the wound environment fosters the advancement of cells within the population that are better fit to migrate and/or proliferate in response to PDGF stimulation. Thus, cell-to-cell variability results in a significantly higher rate of wound invasion as compared with the deterministic model, in a manner that depends on the way in which individual cell properties are sampled or inherited upon cell division.


Authors

Michael I. Monine
Los Alamos National Laboratory
Jason M. Haugh
North Carolina State University

We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.

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