In the 1970's Dr. Judah Folkman, first suggested that the prevention of angiogenesis in cancer tumors could be an effective means of their control and even eradication. Certain drugs (such as angiostaten) have recently been found which do this in mice with remarkable efficiency. This discovery received widespread international press coverage and boosted scientific interest in angiogenesis and highlights the pressing need for an understanding of the biological developmental processes involved. A major part of the research that was proposed in this part of the grant is specifically directed towards this goal. We have been developing and analyzing specific cell-tissue interaction mechanisms for the formation of the complex spatial patterns found in cell-matrix interaction with particular emphasis on cell-Matrigel in vitro experiments. The interaction between the cells and the extracellular matrix (ECM) has been proposed as a key process in angiogenesis. We have been able to determine certain properties which are essential for pattern formation. Since we believe that fibroblast traction forces are major players in angiogenesis we used the Murray-Oster mechanical theory of morphogenesis. It is also the basis for our study of dermal wound healing. The models are based on the mechanical interaction between fibroblasts and the extracellular matrix (ECM). In each study, by numerically simulating two-dimensional configurations and carrying out mathematical analyses of the models we have been able to make predictions about the roles of key parameters including those associated with mitosis, traction and extracellular matrix (ECM) turnover. In the case of cell-Matrigel interactions we have shown that the model system produces patterns which have an astonishing similarity to those found experimentally: the complex network patterns formed by the model solutions are almost indistinguishable from those found in vitro. With regard to wound healing we have been able to show that there is a residual stress in the extracellular matrix as a consequence of the fibroblast deformation. This latter work in reported in Murray et al. (1997).
| Bassingthwaighte, James B; Butterworth, Erik; Jardine, Bartholomew et al. (2012) Compartmental modeling in the analysis of biological systems. Methods Mol Biol 929:391-438 |
| Dash, Ranjan K; Bassingthwaighte, James B (2010) Erratum to: Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels. Ann Biomed Eng 38:1683-701 |
| Bassingthwaighte, James B; Raymond, Gary M; Butterworth, Erik et al. (2010) Multiscale modeling of metabolism, flows, and exchanges in heterogeneous organs. Ann N Y Acad Sci 1188:111-20 |
| Dash, Ranjan K; Bassingthwaighte, James B (2006) Simultaneous blood-tissue exchange of oxygen, carbon dioxide, bicarbonate, and hydrogen ion. Ann Biomed Eng 34:1129-48 |
| Dash, Ranjan K; Bassingthwaighte, James B (2004) Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels. Ann Biomed Eng 32:1676-93 |
| Kellen, Michael R; Bassingthwaighte, James B (2003) Transient transcapillary exchange of water driven by osmotic forces in the heart. Am J Physiol Heart Circ Physiol 285:H1317-31 |
| Kellen, Michael R; Bassingthwaighte, James B (2003) An integrative model of coupled water and solute exchange in the heart. Am J Physiol Heart Circ Physiol 285:H1303-16 |
| Wang, C Y; Bassingthwaighte, J B (2001) Capillary supply regions. Math Biosci 173:103-14 |
| Swanson, K R; True, L D; Lin, D W et al. (2001) A quantitative model for the dynamics of serum prostate-specific antigen as a marker for cancerous growth: an explanation for a medical anomaly. Am J Pathol 158:2195-9 |
| Swanson, K R; Alvord Jr, E C; Murray, J D (2000) A quantitative model for differential motility of gliomas in grey and white matter. Cell Prolif 33:317-29 |
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