TY - JOUR
T1 - Chapter 18 Modeling of Growth Factor-Receptor Systems. From Molecular-Level Protein Interaction Networks to Whole-Body Compartment Models
AU - Wu, Florence T.H.
AU - Stefanini, Marianne O.
AU - Gabhann, Feilim Mac
AU - Popel, Aleksander S.
N1 - Funding Information:
This work was supported by NIH grants R01 HL079653, R33 HL0877351, and R01 CA138264.
PY - 2009
Y1 - 2009
N2 - Most physiological processes are subjected to molecular regulation by growth factors, which are secreted proteins that activate chemical signal transduction pathways through binding of specific cell-surface receptors. One particular growth factor system involved in the in vivo regulation of blood vessel growth is called the vascular endothelial growth factor (VEGF) system. Computational and numerical techniques are well suited to handle the molecular complexity (the number of binding partners involved, including ligands, receptors, and inert binding sites) and multiscale nature (intratissue vs. intertissue transport and local vs. systemic effects within an organism) involved in modeling growth factor system interactions and effects. This chapter introduces a variety of in silico models that seek to recapitulate different aspects of VEGF system biology at various spatial and temporal scales: molecular-level kinetic models focus on VEGF ligand-receptor interactions at and near the endothelial cell surface; mesoscale single-tissue 3D models can simulate the effects of multicellular tissue architecture on the spatial variation in VEGF ligand production and receptor activation; compartmental modeling allows efficient prediction of average interstitial VEGF concentrations and cell-surface VEGF signaling intensities across multiple large tissue volumes, permitting the investigation of whole-body intertissue transport (e.g., vascular permeability and lymphatic drainage). The given examples will demonstrate the utility of computational models in aiding both basic science and clinical research on VEGF systems biology.
AB - Most physiological processes are subjected to molecular regulation by growth factors, which are secreted proteins that activate chemical signal transduction pathways through binding of specific cell-surface receptors. One particular growth factor system involved in the in vivo regulation of blood vessel growth is called the vascular endothelial growth factor (VEGF) system. Computational and numerical techniques are well suited to handle the molecular complexity (the number of binding partners involved, including ligands, receptors, and inert binding sites) and multiscale nature (intratissue vs. intertissue transport and local vs. systemic effects within an organism) involved in modeling growth factor system interactions and effects. This chapter introduces a variety of in silico models that seek to recapitulate different aspects of VEGF system biology at various spatial and temporal scales: molecular-level kinetic models focus on VEGF ligand-receptor interactions at and near the endothelial cell surface; mesoscale single-tissue 3D models can simulate the effects of multicellular tissue architecture on the spatial variation in VEGF ligand production and receptor activation; compartmental modeling allows efficient prediction of average interstitial VEGF concentrations and cell-surface VEGF signaling intensities across multiple large tissue volumes, permitting the investigation of whole-body intertissue transport (e.g., vascular permeability and lymphatic drainage). The given examples will demonstrate the utility of computational models in aiding both basic science and clinical research on VEGF systems biology.
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U2 - 10.1016/S0076-6879(09)67018-X
DO - 10.1016/S0076-6879(09)67018-X
M3 - Review article
C2 - 19897104
AN - SCOPUS:71549172503
SN - 0076-6879
VL - 467
SP - 461
EP - 497
JO - Methods in enzymology
JF - Methods in enzymology
IS - C
ER -