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Published May 18, 2011 | Supplemental Material
Journal Article Open

Protein Signaling Networks from Single Cell Fluctuations and Information Theory Profiling


Protein signaling networks among cells play critical roles in a host of pathophysiological processes, from inflammation to tumorigenesis. We report on an approach that integrates microfluidic cell handling, in situ protein secretion profiling, and information theory to determine an extracellular protein-signaling network and the role of perturbations. We assayed 12 proteins secreted from human macrophages that were subjected to lipopolysaccharide challenge, which emulates the macrophage-based innate immune responses against Gram-negative bacteria. We characterize the fluctuations in protein secretion of single cells, and of small cell colonies (n = 2, 3,···), as a function of colony size. Measuring the fluctuations permits a validation of the conditions required for the application of a quantitative version of the Le Chatelier's principle, as derived using information theory. This principle provides a quantitative prediction of the role of perturbations and allows a characterization of a protein-protein interaction network.

Additional Information

© 2011 Biophysical Society. Submitted December 27, 2010, and accepted for publication April 8, 2011. Young Shik Shin and F. Remacle contributed equally to this work. Editor: Andre Levchenko. This work was supported by National Cancer Institute grant No. 5U54 CA119347 (J.R.H., P.I.), a gift from the Jean Perkins Foundation, and the California Institute of Technology/University of California, Los Angeles, Joint Center for Translational Research. K.H acknowledges the Samsung Scholarship. R.F. acknowledges the support by National Cancer Institute grant No. 1K99 CA136759-01. F.R. is director of Fonds National de la Recherch Scientifique.

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