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

Phuong Le, Sung Jun Lim, Brian C. Baculis, Hee Jung Chung, Kristopher A. Kilian, Andrew M Smith

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number909
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Quantum Dots
stimulation
Semiconductor quantum dots
Intercellular Signaling Peptides and Proteins
counting
quantum dots
Cells
Infrared radiation
cells
Deconvolution
Epidermal Growth Factor
Microscopic examination
Fluorescence
Ligands
Molecules
Triple Negative Breast Neoplasms
breast
inhibitors
drugs
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Counting growth factors in single cells with infrared quantum dots to measure discrete stimulation distributions. / Le, Phuong; Lim, Sung Jun; Baculis, Brian C.; Chung, Hee Jung; Kilian, Kristopher A.; Smith, Andrew M.

In: Nature communications, Vol. 10, No. 1, 909, 01.12.2019.

Research output: Contribution to journalArticle

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