BIOPHYSICAL THEORY AND MODELING |
Deterministic Model of Dermal Wound Invasion Incorporating Receptor-mediated Signal Transduction and Spatial Gradient Sensing
Jason M. Haugh 1*
1 North Carolina State University
* To whom correspondence should be addressed. E-mail: jason_haugh{at}ncsu.edu.
Submitted on November 11, 2005
Revised on December 14, 2005
Accepted on 23 December 2005
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Abstract |
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During dermal wound healing, platelet-derived growth factor (PDGF) serves as both a chemoattractant and mitogen for fibroblasts, potently stimulating their invasion of the fibrin clot over a period of several days. A mathematical model of this process is presented, which accurately accounts for the sensitivity of PDGF gradient sensing through PDGF receptor/phosphoinositide (PI) 3-kinase-mediated signal transduction. Analysis of the model suggests that PDGF receptor-mediated endocytosis and degradation of PDGF allows a constant PDGF concentration profile to be maintained at the leading front of the fibroblast density profile as it propagates, at a constant rate, into the clot. Thus, the constant PDGF gradient can span the optimal concentration range for asymmetric PI 3-kinase signaling and fibroblast chemotaxis, with near-maximal invasion rates elicited over a relatively broad range of PDGF secretion rates. A somewhat surprising finding was that extremely sharp PDGF gradients do not necessarily stimulate faster progression through the clot, because maintaining such a gradient through PDGF consumption is a potentially rate-limiting process.
Key Words:
Mathematical model, PDGF, cell migration, chemotaxis, gradient, receptor
