Protein signaling networks from single cell fluctuations and information theory profiling

Young Shik Shin, F. Remacle, Rong Fan, Kiwook Hwang, Wei Wei, Habib Ahmad, R. D. Levine, James R. Heath

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2378-2386
Number of pages9
JournalBiophysical Journal
Volume100
Issue number10
DOIs
StatePublished - 18 May 2011

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