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Cellular signaling is potentially regulated by cell density in receptor trafficking networks
Authors:Zi Zhike  Klipp Edda
Affiliation:Computational Systems Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse. 73, 14195 Berlin, Germany. zhike_zi@molgen.mpg.de
Abstract:Previous work has shown that receptor trafficking is a potential site for the control of signaling pathways. In most biological experiments, the ligand concentration and cell density vary within a wide range among different systems. However, there is less attention to systematically analyze how much cellular signal response is affected by cell densities. Here, we use a quantitative mathematical model to investigate signal responses in different receptor trafficking networks by simultaneous variations of ligand concentration and cell density. Computational analysis of the model revealed that receptor trafficking networks have potential sigmoid responses to ratio between ligand and surface receptor number per cell, which is a key factor to control the signaling responses in receptor trafficking networks. Furthermore, cell density also affects the robustness of dose-response curve upon the variation of binding affinity.
Keywords:EGF, epidermal growth factor   LRs, surface ligand-receptor complex   LRi, internalized ligand-receptor complex   RLRs ratio, ratio between ligand and surface receptor number per cell
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