Cell population-based model of dermal wound invasion with heterogeneous intracellular signaling properties.
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; 90:2297-308). 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.
Monine
Michael I
MI
Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, New Mexico, USA.
Haugh
Jason M
JM
D002470:Cell Survival; D002633:Chemotaxis; D005347:Fibroblasts; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000293:injuries / Q000378:metabolism* / Q000473:pathology*; D013379:Substrate Specificity
D019869:Phosphatidylinositol 3-Kinases; D017479:Receptors, Platelet-Derived Growth Factor