A Noisy Paracrine Signal Determines the Cellular NF-κB Response to Lipopolysaccharide

Timothy K. Lee, Elissa M. Denny, Jayodita C. Sanghvi, Jahlionais E. Gaston, Nathaniel D. Maynard, Jacob J. Hughey, Markus W. Covert*

*To whom correspondence should be addressed. E-mail: mcovert{at}stanford.edu

This PDF file includes:

• Fig. S1. Lentiviral expression construct and activation of NF-κB in cells reconstituted with EGFP-p65.
• Fig. S2. Metrics of variability in the TNF-α response.
• Fig. S3. Parameter fitting to single-cell data.
• Fig. S4. Clonal cells stimulated with LPS.
• Fig. S5. Cells unresponsive to LPS.
• Fig. S6. Lack of correlation between NF-κB dynamics and spatial location.
• Fig. S7. TLR4^del MEFs (EGFP-p65) treated with LPS.
• Fig. S8. TLR4^del MEFs (EGFP-p65) treated with TNF-α.
• Fig. S9. TLR4^del MEFs (EGFP-p65) cultured with wild-type MEFs and treated with LPS and soluble TNFR (sTNFRII).
• Fig. S10. Coculture plating density influences the activation of NF-κB in TLR^del cells.
• Fig. S11. Trif^–/– MEFs exposed to LPS.
• Fig. S12. MyD88^–/– MEFs exposed to LPS.
• Fig. S13. Total cellular fluorescence during a typical experiment.
• Fig. S14. Single-cell fit distances compared to global variation between cells.
• Table S1. Parameter distributions from single-cell fitting.

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Supplementary Material for this manuscript includes the following:

MATLAB files for simulations

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Citation: T. K. Lee, E. M. Denny, J. C. Sanghvi, J. E. Gaston, N. D. Maynard, J. J. Hughey, M. W. Covert, A noisy paracrine signal determines the cellular NF-κB response to lipopolysaccharide. Sci. Signal. 2, ra65 (2009).

© 2009 American Association for the Advancement of Science