title: Chemical methods for the simultaneous quantitation of metabolites and proteins from single cells.
abstract: We describe chemical approaches for integrated metabolic and proteomic assays from single cells. Quantitative assays for intracellular metabolites, including glucose uptake and three other species, are designed as surface-competitive binding assays with fluorescence readouts. This enables integration into a microarray format with functional protein immunoassays, all of which are incorporated into the microchambers of a single-cell barcode chip (SCBC). By using the SCBC, we interrogate the response of human-derived glioblastoma cancer cells to epidermal growth factor receptor inhibition. We report, for the first time, on both the intercellular metabolic heterogeneity as well as the baseline and drug-induced changes in the metabolite-phosphoprotein correlation network.
authors: †Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
authors: Min
authors: M
authors: Xue
authors: ‡Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095, United States.
authors: Wei
authors: W
authors: Wei
authors: †Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
authors: Yapeng
authors: Y
authors: Su
authors: †Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
authors: Jungwoo
authors: J
authors: Kim
authors: ‡Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095, United States.
authors: Young Shik
authors: YS
authors: Shin
authors: ‡Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095, United States.
authors: Wilson X
authors: WX
authors: Mai
authors: ‡Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095, United States.
authors: David A
authors: DA
authors: Nathanson
authors: †Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.|‡Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095, United States.
authors: James R
authors: JR
authors: Heath
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride / Q000494:pharmacology; D005455:Fluorescent Antibody Technique / Q000295:instrumentation / Q000379:methods; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D055432:Metabolomics / Q000295:instrumentation* / Q000379:methods; D046228:Microarray Analysis / Q000295:instrumentation* / Q000379:methods; D040901:Proteomics / Q000295:instrumentation* / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors