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Counting growth factors in single cells with infrared quantum dots to measure discrete stimulation distributions

Title
Counting growth factors in single cells with infrared quantum dots to measure discrete stimulation distributions
Author(s)
Le, PhuongLim, Sung JunBaculis, Brian C.Chung, Hee JungKilian, Kristopher A.Smith, Andrew M.
Issued Date
2019-02
Citation
Nature Communications, v.10, no.1
Type
Article
Keywords
FACTOR RECEPTORGENE-EXPRESSIONEGFRMOLECULEORIGINSTUMORVARIABILITYACTIVATIONMECHANISMSTHERAPIES
ISSN
2041-1723
Abstract
The distribution of single-cell properties across a population of cells can be measured using diverse tools, but no technology directly quantifies the biochemical stimulation events regulating these properties. Here we report digital counting of growth factors in single cells using fluorescent quantum dots and calibrated three-dimensional deconvolution microscopy (QDC-3DM) to reveal physiologically relevant cell stimulation distributions. We calibrate the fluorescence intensities of individual compact quantum dots labeled with epidermal growth factor (EGF) and demonstrate the necessity of near-infrared emission to overcome intrinsic cellular autofluoresence at the single-molecule level. When applied to human triple-negative breast cancer cells, we observe proportionality between stimulation and both receptor internalization and inhibitor response, reflecting stimulation heterogeneity contributions to intrinsic variability. We anticipate that QDC-3DM can be applied to analyze any peptidic ligand to reveal single-cell correlations between external stimulation and phenotypic variability, cell fate, and drug response. © 2019, The Author(s).
URI
http://hdl.handle.net/20.500.11750/9637
DOI
10.1038/s41467-019-08754-5
Publisher
Nature Publishing Group
Related Researcher
Files in This Item:
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000459403800014.pdf

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Appears in Collections:
Division of Nanotechnology 1. Journal Articles

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