title: Protein signaling networks from single cell fluctuations and information theory profiling.
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.
authors.affiliation: Nanosystems Biology Cancer Center and Kavli Nanoscience Institute, California Institute of Technology, Pasadena, California, USA.
authors.forename: Young Shik
authors.initials: YS
authors.lastname: Shin
authors.forename: F
authors.initials: F
authors.lastname: Remacle
authors.forename: Rong
authors.initials: R
authors.lastname: Fan
authors.forename: Kiwook
authors.initials: K
authors.lastname: Hwang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Habib
authors.initials: H
authors.lastname: Ahmad
authors.forename: R D
authors.initials: RD
authors.lastname: Levine
authors.forename: James R
authors.initials: JR
authors.lastname: Heath
mesh_terms: D057134:Antibodies, Neutralizing / Q000378:metabolism; D002460:Cell Line; D003114:Colony-Forming Units Assay; D006801:Humans; D007257:Information Theory; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D057134:Antibodies, Neutralizing; D016209:Interleukin-8; D008070:Lipopolysaccharides