Cells sense external signal constantly, process it, and make its life-determining decision by using the embedded signal processing facilities. All of those events take place within an individual cell and thus should be studied at the level of single cells. Technical advances in live cell imaging make it possible to observe the time evolution of a protein abundance in single cells. Here we use a computational model, live cell fluorescence microscopy, and quantitative RT-PCR to investigate the translocation dynamics of a protein NF-kB and its biological relevance in single macrophages (RAW264.7 cells) when the cells are stimulated by E. coli lipopolysaccharide persistently. We incorporate into the computational model the signaling pathways of TLR4-MyD88-NF-kB, TNF-R and TNFa autocrine signaling and simulate heterogeneous NF-kB response in single cells, by taking into account the cell-to-cell variability in key protein copy numbers and kinetic rate constants. We present the fascinating yet puzzling NF-kB translocation dynamics as a response to different dosage of E. coli lipopolysaccharide: homogeneous oscillatory patterns of NF-kB for a large dosage and heterogeneous monotone-increasing patterns for a small dosage .
This paper has been withdrawn by the author .
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Cells sense external signal constantly, process it, and make its life-determining decision by using the embedded signal processing facilities. All of those events take place within an individual cell and thus should be studied at the level of single cells. Technical advances in live cell imaging make it possible to observe the time evolution of a protein abundance in single cells. Here we use a computational model, live cell fluorescence microscopy, and quantitative RT-PCR to investigate the translocation dynamics of a protein NF-kB and its biological relevance in single macrophages (RAW264.7 cells) when the cells are stimulated by E. coli lipopolysaccharide persistently. We incorporate into the computational model the signaling pathways of TLR4-MyD88-NF-kB, TNF-R and TNFa autocrine signaling and simulate heterogeneous NF-kB response in single cells, by taking into account the cell-to-cell variability in key protein copy numbers and kinetic rate constants. We present the fascinating yet puzzling NF-kB translocation dynamics as a response to different dosage of E. coli lipopolysaccharide: homogeneous oscillatory patterns of NF-kB for a large dosage and heterogeneous monotone-increasing patterns for a small dosage
This paper has been withdrawn by the author