John Dallon: Paper Abstract
Modeling the Effects of TGFbeta on Extracellular Matrix Alignment in Dermal Wound Repair
AUTHORS:
John C. Dallon 1, Jonathan. A. Sherratt 2 and Philip K. Maini 3
1: Department of Mathematics, Brigham Young University,
Provo, UT 84602
2: Department of Mathematics, Heriot-Watt University,
Edinburgh EH14 4AS, UK
3: Centre for Mathematical Biology,
Mathematical Institute,
University of Oxford,
24-29 St Giles',
Oxford OX1 3LB, UK
ABSTRACT:
We present a novel mathematical model for collagen deposition and
alignment during dermal wound healing, focusing on the regulatory
effects of TGFbeta.. Our work extends a previously developed model
which considers the interactions between fibroblasts and
extracellular matrix, composed of collagen and a fibrin based blood
clot, by allowing fibroblasts to orient the collagen matrix, and
produce and degrade the extracellular matrix, while the matrix can
direct the fibroblasts and control their speed. Here we extend the
model by allowing a time varying concentration of TGFbeta to alter
the properties of the fibroblasts. Thus we are able to simulate
experiments which alter the TGFbeta profile. Within this model
framework we find that most of the known effects of TGFbeta, i.e.,
changes in cell motility, cell proliferation and collagen
production, are of minor importance to matrix alignment and cannot
explain the anti-scarring properties of TGFbeta. However, we find
that by changing fibroblast reorientation rates, consistent with
experimental evidence, the alignment of the regenerated tissue can
be significantly altered. This provides an explanation for the
experimentally observed influence of TGFbeta on scarring.
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