Protein Signaling Networks from Single Cell Fluctuations and Information Theory Profiling
Protein Signaling Networks from Single Cell Fluctuations and Information Theory Profiling
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DOI：
10.1016/j.bpj.2011.04.025
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发表时间：
2011-05-18
影响因子：
3.4
通讯作者：
Heath, James R.
中科院分区：
文献类型：
--
作者：
Shin, Young Shik;Remacle, F.;Heath, James R.
细胞间的蛋白质信号网络在从炎症到肿瘤发生的许多病理生理过程中起着关键作用。我们报告的方法，集成微流控细胞处理，原位蛋白质分泌分析，和信息理论，以确定细胞外蛋白质信号网络和扰动的作用。我们测定了12种蛋白质分泌的人巨噬细胞进行脂多糖的挑战，这模拟了巨噬细胞为基础的先天性免疫反应，对革兰氏阴性菌。我们表征了单细胞和小细胞集落（n = 2，3，.），作为菌落大小的函数。测量的波动允许验证所需的条件的应用程序的定量版本的勒Chatelier的原则，使用信息理论推导。这一原则提供了一个定量预测的扰动的作用，并允许一个蛋白质-蛋白质相互作用网络的表征。
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.