Label-free imaging of histamine mediated G protein-coupled receptors activation in live cells

Jin Lu, Yunze Yang, Wei Wang, Jinghong Li, Nongjian Tao, Shaopeng Wang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

G protein-coupled receptors (GPCRs) are the largest protein family for cell signal transduction, and most of them are crucial drug targets. Conventional label-free assays lack the spatial information to address the heterogeneous response from single cells after GPCRs activation. Here, we reported a GPCRs study in live cells using plasmonic-based electrochemical impedance microscopy. This label-free optical imaging platform is able to resolve responses from individual cells with subcellular resolution. Using this platform, we studied the histamine mediated GPCRs activation and revealed spatiotemporal heterogeneity of cellular downstream responses. Triphasic responses were observed from individual HeLa cells upon histamine stimulation. A quick peak P1 in less than 10 s was attributed to the GPCRs triggered calcium release. An inverted P2 phase within 1 min was attributed to the alternations of cell-matrix adhesion after the activation of Protein Kinase C (PKC). The main peak (P3) around 3-6 min after the histamine treatment was due to dynamic mass redistribution and showed a dosedependent response with a half-maximal effective concentration (EC50) of 3.9 ± 1.2 μM. Heterogeneous P3 responses among individual cells were observed, particularly at high histamine concentration, indicating diverse histamine H1 receptor expression level in the cell population.

Original languageEnglish (US)
Pages (from-to)11498-11503
Number of pages6
JournalAnalytical Chemistry
Volume88
Issue number23
DOIs
StatePublished - Dec 6 2016

ASJC Scopus subject areas

  • Analytical Chemistry

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