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Originally published as Biophys J. BioFAST on January 13, 2006.
doi:10.1529/biophysj.105.077610
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Biophysical Journal 90:2297-2308 (2006)
© 2006 The Biophysical Society

Deterministic Model of Dermal Wound Invasion Incorporating Receptor-Mediated Signal Transduction and Spatial Gradient Sensing

Jason M. Haugh

Department of Chemical & Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27695

Correspondence: Address reprint requests to Jason M. Haugh, Tel.: 919-513-3851; Fax: 919-515-3465; E-mail: jason_haugh{at}ncsu.edu.

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 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 phosphoinositide 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.






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Copyright © 2006 by the Biophysical Society.