Modeling of growth factor-receptor systems from molecular-level protein interaction networks to whole-body compartment models.

摘要: Most physiological processes are subjected to molecular regulation by growth factors, which secreted proteins that activate chemical signal transduction pathways through binding of specific cell-surface receptors. One particular factor system involved in the vivo blood vessel is called vascular endothelial (VEGF) system. Computational and numerical techniques well suited handle complexity (the number partners involved, including ligands, receptors, inert sites) multiscale nature (intratissue vs. intertissue transport local systemic effects within an organism) modeling interactions effects. This chapter introduces a variety silico models seek recapitulate different aspects VEGF biology at various spatial temporal scales: molecular-level kinetic focus on ligand–receptor near cell surface; mesoscale single-tissue 3D can simulate multicellular tissue architecture variation ligand production receptor activation; compartmental allows efficient prediction average interstitial concentrations signaling intensities across multiple large volumes, permitting investigation whole-body (e.g., permeability lymphatic drainage). The given examples will demonstrate utility computational aiding both basic science clinical research systems biology.