Chapter 18 Modeling of Growth Factor-Receptor Systems. From Molecular-Level Protein Interaction Networks to Whole-Body Compartment Models

Florence T H Wu, Marianne O. Stefanini, Feilim Mac Gabhann, Aleksander S Popel

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)461-497
Number of pages37
JournalMethods in Enzymology
Volume467
Issue numberC
DOIs
StatePublished - 2009

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Protein Interaction Maps
Growth Factor Receptors
Vascular Endothelial Growth Factor A
Intercellular Signaling Peptides and Proteins
Proteins
Systems Biology
Ligands
Tissue
Physiological Phenomena
Vascular Endothelial Growth Factor Receptor
Capillary Permeability
Cell Surface Receptors
Signal transduction
Endothelial cells
Computer Simulation
Blood vessels
Blood Vessels
Drainage
Signal Transduction
Endothelial Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Chapter 18 Modeling of Growth Factor-Receptor Systems. From Molecular-Level Protein Interaction Networks to Whole-Body Compartment Models. / Wu, Florence T H; Stefanini, Marianne O.; Gabhann, Feilim Mac; Popel, Aleksander S.

In: Methods in Enzymology, Vol. 467, No. C, 2009, p. 461-497.

Research output: Contribution to journalArticle

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