ArticlePloS one2009
Coupled stochastic spatial and non-spatial simulations of ErbB1 signaling pathways demonstrate the importance of spatial organization in signal transduction.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Confined diffusion of transmembrane proteins and lipids induced by the same actin meshwork lining the plasma membrane.Molecular biology of the cell · 2016Article
- Effect of Spatial Inhomogeneities on the Membrane Surface on Receptor Dimerization and Signal Initiation.Frontiers in cell and developmental biology · 2016Article
- Mathematical modelling and computational study of two-dimensional and three-dimensional dynamics of receptor-ligand interactions in signalling response mechanisms.Journal of mathematical biology · 2014Article
- Dynamic transition states of ErbB1 phosphorylation predicted by spatial stochastic modeling.Biophysical journal · 2013Article
- The impact of high density receptor clusters on VEGF signaling.Electronic proceedings in theoretical computer science · 2013Article
- Mathematical simulation of membrane protein clustering for efficient signal transduction.Annals of biomedical engineering · 2012Review
- Hybrid spatial Gillespie and particle tracking simulation.Bioinformatics (Oxford, England) · 2012Article
- Spatial simulations in systems biology: from molecules to cells.International journal of molecular sciences · 2012Review
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- An adaptive coarse graining method for signal transduction in three dimensions.Fundamenta informaticae · 2012Article
- Modeling formalisms in Systems Biology.AMB Express · 2011Article
- Balancing forces: architectural control of mechanotransduction.Nature reviews. Molecular cell biology · 2011Review
- Macroscopic law of conservation revealed in the population dynamics of Toll-like receptor signaling.Cell communication and signaling : CCS · 2011Article
- Spatial aspects in biological system simulations.Methods in enzymology · 2011Article
- Quantitative understanding of cell signaling: the importance of membrane organization.Current opinion in biotechnology · 2010Review
- A multiscale systems perspective on cancer, immunotherapy, and Interleukin-12.Molecular cancer · 2010Review
- Towards a matrix mechanics framework for dynamic protein network.Systems and synthetic biology · 2010Article
- Spatially distributed cell signalling.FEBS letters · 2009Review
- Analytical solution of steady-state equations for chemical reaction networks with bilinear rate laws.IEEE/ACM transactions on computational biology and bioinformaticsArticle
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Authors and funding
5 authors.
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Abstract
backgroundThe ErbB family of receptors activates intracellular signaling pathways that control cellular proliferation, growth, differentiation and apoptosis. Given these central roles, it is not surprising that overexpression of the ErbB receptors is often associated with carcinogenesis. Therefore, extensive laboratory studies have been devoted to understanding the signaling events associated with ErbB activation. METHODOLOGY/PRINCIPAL
findingsSystems biology has contributed significantly to our current understanding of ErbB signaling networks. However, although computational models have grown in complexity over the years, little work has been done to consider the spatial-temporal dynamics of receptor interactions and to evaluate how spatial organization of membrane receptors influences signaling transduction. Herein, we explore the impact of spatial organization of the epidermal growth factor receptor (ErbB1/EGFR) on the initiation of downstream signaling. We describe the development of an algorithm that couples a spatial stochastic model of membrane receptors with a nonspatial stochastic model of the reactions and interactions in the cytosol. This novel algorithm provides a computationally efficient method to evaluate the effects of spatial heterogeneity on the coupling of receptors to cytosolic signaling partners. CONCLUSIONS/SIGNIFICANCE: Mathematical models of signal transduction rarely consider the contributions of spatial organization due to high computational costs. A hybrid stochastic approach simplifies analyses of the spatio-temporal aspects of cell signaling and, as an example, demonstrates that receptor clustering contributes significantly to the efficiency of signal propagation from ligand-engaged growth factor receptors.
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