Skip to main content

Advertisement

SpringerLink
Log in

Interrogating the variation of element masses and distribution patterns in single cells using ICP-MS with a high efficiency cell introduction system

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Cellular heterogeneity is an inherent condition of cell populations, which results from stochastic expression of genes, proteins, and metabolites. The heterogeneity of individual cells can dramatically influence cellular decision-making and cell fate. So far, our knowledge about how the variation of endogenous metals and non-metals in individual eukaryotic cells is limited. In this study, ICP-MS equipped with a high efficiency cell introduction system (HECIS) was developed as a method of single-cell ICP-MS (SC-ICP-MS). The method was applied to the single-cell analysis of Mn, Fe, Co, Cu, Zn, P, and S in human cancer cell lines (HeLa and A549) and normal human bronchial epithelial cell line (16HBE). The analysis showed obvious variation of the masses of Cu, Fe, Zn, and P in individual HeLa cells, and variation of Fe, Zn, and P in individual A549 cells. On the basis of the single-cell data, a multimodal distribution of the elements in the cell population was fitted, which showed marked differences among the various cell lines. Importantly, subpopulations of the elements were found in the cell populations, especially in the HeLa cancer cells. This study demonstrates that SC-ICP-MS is able to unravel the extent of variation of endogenous elements in individual cells, which will help to improve our fundamental understanding of cellular biology and reveal novel insights into human biology and medicine.

The variations of masses and distribution patterns of elements Mn, Fe, Co, Cu, Zn, P, and S in single cells were successfully detected by ICP-MS coupled with a high efficiency cell introduction system (HECIS)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Haraguchi H. Metallomics as integrated biometal science. J Anal Atom Spectrom. 2004;19:5–14.

    Article  CAS  Google Scholar 

  2. Waldron KJ, Rutherford JC, Ford D, Robinson NJ. Metalloproteins and metal sensing. Nature. 2009;460:823–30.

    Article  CAS  Google Scholar 

  3. Wang DJ, Bodovitz S. Single cell analysis: the new frontier in 'omics'. Trends Biotechnol. 2010;28:281–90.

    Article  CAS  Google Scholar 

  4. Cai L, Friedman N, Xie XS. Stochastic protein expression in individual cells at the single molecule level. Nature. 2006;440:358–62.

    Article  CAS  Google Scholar 

  5. Kaern M, Elston TC, Blake WJ, Collins JJ. Stochasticity in gene expression: from theories to phenotypes. Nat Rev Genet. 2005;6:451–64.

    Article  CAS  Google Scholar 

  6. Schubert C. Single-cell analysis: the deepest differences. Nature. 2011;480:133–7.

    Article  CAS  Google Scholar 

  7. Zunder ER, Lujan E, Goltsev Y, Wernig M, Nolan GP. A continuous molecular roadmap to iPSC reprogramming through progression analysis of single-cell mass cytometry. Cell Stem Cell. 2015;16:323–37.

    Article  CAS  Google Scholar 

  8. Behbehani GK, Bendall SC, Clutter MR, Fantl WJ, Nolan GP. Single-cell mass cytometry adapted to measurements of the cell cycle. Cytometry A. 2012;81:552–66.

    Article  Google Scholar 

  9. Chang Q, Ornatsky OI, Koch CJ, Chaudary N, Marie-Egyptienne DT, Hill RP, et al. Single-cell measurement of the uptake, intratumoral distribution and cell cycle effects of cisplatin using mass cytometry. Int J Cancer. 2015;136:1202–9.

    Article  CAS  Google Scholar 

  10. Bendall SC, Simonds EF, Qiu P, Amir ED, Krutzik PO, Finck R, et al. Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science. 2011;332:687–96.

    Article  CAS  Google Scholar 

  11. Drescher D, Giesen C, Traub H, Panne U, Kneipp J, Jakubowski N. Quantitative imaging of gold and silver nanoparticles in single eukaryotic cells by laser ablation ICP-MS. Anal Chem. 2012;84:9684–8.

    Article  CAS  Google Scholar 

  12. Managh AJ, Edwards SL, Bushell A, Wood KJ, Geissler EK, Hutchinson JA, et al. Single cell tracking of gadolinium labeled CD4+ T cells by laser ablation inductively coupled plasma mass spectrometry. Anal Chem. 2013;85:10627–34.

    Article  CAS  Google Scholar 

  13. Wang M, Zheng LN, Wang B, Chen HQ, Zhao YL, Chai ZF, et al. Quantitative analysis of gold nanoparticles in single cells by laser ablation inductively coupled plasma-mass spectrometry. Anal Chem. 2014;86:10252–6.

    Article  CAS  Google Scholar 

  14. Van Malderen SJM, Vergucht E, De Rijcke M, Janssen C, Vincze L, Vanhaecke F. Quantitative Determination and subcellular imaging of Cu in single cells via laser ablation-ICP-mass spectrometry using high-density microarray gelatin standards. Anal Chem. 2016;88:5783–9.

    Article  Google Scholar 

  15. Degueldre C, Favarger PY. Colloid analysis by single particle inductively coupled plasma-mass spectroscopy: a feasibility study. Colloid Surface A. 2003;217:137–42.

    Article  CAS  Google Scholar 

  16. Zheng LN, Wang M, Wang B, Chen HQ, Ouyang H, Zhao YL, et al. Determination of quantum dots in single cells by inductively coupled plasma mass spectrometry. Talanta. 2013;116:782–7.

    Article  CAS  Google Scholar 

  17. Ho KS, Chan WT. Time-resolved ICP-MS measurement for single-cell analysis and on-line cytometry. J Anal Atom Spectrom. 2010;25:1114–22.

    Article  CAS  Google Scholar 

  18. Laborda F, Jiménez-Lamana J, Bolea E, Castillo JR. Selective identification, characterization and determination of dissolved silver(i) and silver nanoparticles based on single particle detection by inductively coupled plasma mass spectrometry. J Anal Atom Spectrom. 2011;26:1362–71.

    Article  CAS  Google Scholar 

  19. Nomizu T, Kaneco S, Tanaka T, Ito D, Kawaguchi H, Vallee BT. Determination of calcium content in individual biological cells by inductively-coupled plasma-atomic emission-spectrometry. Anal Chem. 1994;66:3000–4.

    Article  CAS  Google Scholar 

  20. Pace HE, Rogers NJ, Jarolimek C, Coleman VA, Higgins CP, Ranville JF. Determining transport efficiency for the purpose of counting and sizing nanoparticles via single particle inductively coupled plasma mass spectrometry. Anal Chem. 2011;83:9361–9.

    Article  CAS  Google Scholar 

  21. Groombridge AS, Miyashita S, Fujii S, Nagasawa K, Okahashi T, Ohata M, et al. High sensitive elemental analysis of single yeast cells (Saccharomyces cerevisiae) by time-resolved inductively-coupled plasma mass spectrometry using a high efficiency cell introduction system. Anal Sci. 2013;29:597–603.

    Article  CAS  Google Scholar 

  22. Shigeta K, Koellensperger G, Rampler E, Traub H, Rottmann L, Panne U, et al. Sample introduction of single selenized yeast cells (Saccharomyces cerevisiae) by micro droplet generation into an ICP-sector field mass spectrometer for label-free detection of trace elements. J Anal Atom Spectrom. 2013;28:637–45.

    Article  CAS  Google Scholar 

  23. Wang HL, Wang B, Wang M, Zheng LN, Chen HQ, Chai ZF, et al. Time-resolved ICP-MS analysis of mineral element contents and distribution patterns in single cells. Analyst. 2015;140:523–31.

    Article  CAS  Google Scholar 

  24. Cheng HY, Yin XF, Xu ZG, Wang XZ, Shen H. A simple and demountable capillary microflow nebulizer with a tapered tip for inductively coupled plasma mass spectrometry. Talanta. 2011;85:794–9.

    Article  CAS  Google Scholar 

  25. Finney L, Vogt S, Fukai T, Glesne D. Copper and angiogenesis: unravelling a relationship key to cancer progression. Clin Exp Pharmacol Physiol. 2009;36:88–94.

    Article  CAS  Google Scholar 

  26. MacDonald RS. The role of zinc in growth and cell proliferation. J Nutr. 2000;13:1500S–8.

    Google Scholar 

  27. Sieprawska A, Filek M, Tobiasz A, Walas S, Dudek-Adamska D, Grygo-Szymanko E. Trace elements’ uptake and antioxidant response to excess of manganese in in vitro cells of sensitive and tolerant wheat. Acta Physiol Plant. 2016;38:55.

    Article  Google Scholar 

  28. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008;7:11–20.

    Article  CAS  Google Scholar 

  29. Botto RI, Zhu JJ. Use of an ultrasonic nebulizer with membrane desolvation for analysis of volatile solvents by inductively coupled plasma atomic emission spectrometry. J Anal Atom Spectrom. 1994;9:905–12.

    Article  CAS  Google Scholar 

  30. Asfaw A, Beauchemin D. Improvement of the capabilities of inductively coupled plasma optical emission spectrometry by replacing the desolvation system of an ultrasonic nebulization system with a pre-evaporation tube. Spectrochim Acta B. 2010;65:376–84.

    Article  Google Scholar 

  31. Torti SV, Torti FM. Iron and cancer: more ore to be mined. Nat Rev Cancer. 2013;13:342–55.

    Article  CAS  Google Scholar 

  32. Torti SV, Torti FM. Ironing out cancer. Cancer Res. 2011;71:1511–4.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Thanks for the financial support from the National Basic Research Program (2016YFA0201603), Key Program of Joint Funds of National Natural Science Foundation of China (U1432245), and the National Natural Science Foundation of China (11475195, 11275214, and 11375211).

Author information

Authors and Affiliations

  1. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, 19B, Yu Quan Road, Shijingshan District, Beijing, 100049, China

    Hailong Wang, Meng Wang, Bing Wang, Lingna Zheng, Hanqing Chen, Zhifang Chai & Weiyue Feng

Authors
  1. Hailong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Meng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lingna Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hanqing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhifang Chai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Weiyue Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Weiyue Feng.

Ethics declarations

Conflict of interest

The authors declare that they have no potential conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 436 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, H., Wang, M., Wang, B. et al. Interrogating the variation of element masses and distribution patterns in single cells using ICP-MS with a high efficiency cell introduction system. Anal Bioanal Chem 409, 1415–1423 (2017). https://doi.org/10.1007/s00216-016-0075-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-016-0075-y

Keywords

Search

Navigation