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The purpose of this research is to develop a computer program that models both the stochastic and the deterministic components of cell-cell or cell-extracellular matrix interactions and how they are affected by cells biological processes. This application is in response to the National Institute of Mental Health’s Program Announcement on Computational Neuroscience (PA-97-006). The program will be the first to combine the biological foundations of intercellular communication theory as presented in the project on Cell-cell or cell-extracellular matrix interaction, by the project on Stochastic Ca2+ Signals, by the project on Growth Factors, by the project on Growth Control by Membrane Receptors, and by the project on Growth Factor and Membrane Receptor Systems (NCI LCCC CCSG P30 CA21765). The model will be built using a component-based object-oriented method, which will make use of the new open source object-oriented programming technology, GULP. The specific objectives of the modeling projects are: (1) To develop an agent-based model for the Cell-Cell or cell-extracellular matrix interactions (2) To develop a model for the production and degradation of a growth factor and its regulated cell signaling pathways, (3) To develop a model for growth factor-bound receptor signaling pathways that trigger cellular responses, (4) To develop a model for intracellular Ca2+ dynamics and to explore the relationships between growth factor-mediated Ca2+ changes and the mitogen-activated protein kinase cascade, and (5) To develop a mathematical model for cell growth in an extracellular matrix, which explicitly incorporates both matrix-borne and soluble growth factors. In Aim 2, the model will be used to simulate cell-cell and cell-matrix interactions using a mechanistically based cell-cell signaling model, introduced in this R&D award. The

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