Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

PHOTOACOUSTIC MICROSCOPY

Imaging intratumoral metabolic heterogeneity

Nature Biomedical Engineering volume 3, pages 333–334 (2019)Cite this article

Subjects

The oxygen consumption rates of single tumour cells can be measured via photoacoustic microscopy, by leveraging haemoglobin as both an oxygen supplier and an oxygen sensor.

Cellular metabolism is closely coupled to cell function. For example, cancer cells can reprogram their metabolism to fuel proliferation, even in the absence of growth-factor signals. Also, individual tumour cells have varying metabolic adaptations in response to the unique levels of nutrients, cytokines, oxygen and pH available in their microenvironment1. The mechanisms of adaptation used by tumour cells can affect their sensitivity to drugs, and even provide potential targets for treatment2. The ability to evaluate intratumoral heterogeneity is thus essential, because drug-resistant subpopulations of tumour cells within an overall drug-responsive tumour can lead to treatment failure and cancer recurrence3. The cell-level diversity of metabolic adaptation highlights the need for tools that can measure metabolic heterogeneity in tumour cells. Reporting in Nature Biomedical Engineering, Jun Zou, Lihong Wang and colleagues now show that the oxygen consumption rates (OCRs) of single cells deposited in microwell arrays can be measured via photoacoustic microscopy (PAM), by using haemoglobin as both an oxygen supplier and an oxygen sensor4 (Fig. 1).

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Fig. 1: Photoacoustic microscopy quantifies single-cell oxygen consumption in microwell arrays.

References

  1. Vander Heiden, M. G. et al. Cold Spring Harb. Symp. Quant. Biol. 76, 325–334 (2011).

    Article  Google Scholar 

  2. Vander Heiden, M. G. Nat. Rev. Drug Discov. 10, 671–684 (2011).

    Article  Google Scholar 

  3. Marusyk, A. & Polyak, K. Biochim. Biophys. Acta 1805, 105–117 (2010).

    CAS  PubMed  Google Scholar 

  4. Hai, P. et al. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-019-0376-5 (2019).

    Article  PubMed  Google Scholar 

  5. Zhang, H. F., Maslov, K., Stoica, G. & Wang, L. V. Nat. Biotechnol. 24, 848–851 (2006).

    CAS  Article  Google Scholar 

  6. Alhallak, K., Rebello, L. G., Muldoon, T. J., Quinn, K. P. & Rajaram, N. Biomed. Opt. Express 7, 4364–4374 (2016).

    CAS  Article  Google Scholar 

  7. Hou, J. et al. J. Biomed. Opt. 21, 60503 (2016).

    Article  Google Scholar 

  8. Shah, A. T., Diggins, K. E., Walsh, A. J., Irish, J. M. & Skala, M. C. Neoplasia 17, 862–870 (2015).

    CAS  Article  Google Scholar 

  9. Walsh, A. J. & Skala, M. C. Biomed. Opt. Express 6, 559–573 (2015).

    Article  Google Scholar 

  10. Walsh, A. J. et al. Cancer Res. 74, 5184–5194 (2014).

    CAS  Article  Google Scholar 

  11. O’Neil, R. G., Wu, L. & Mullani, N. Mol. Imaging Biol. 7, 388–392 (2005).

    Article  Google Scholar 

  12. Tantama, M., Hung, Y. P. & Yellen, G. J. Am. Chem. Soc. 133, 10034–10037 (2011).

    CAS  Article  Google Scholar 

  13. Poburko, D., Santo-Domingo, J. & Demaurex, N. J. Biol. Chem. 286, 11672–11684 (2011).

    CAS  Article  Google Scholar 

  14. Howard, S. S., Straub, A., Horton, N., Kobat, D. & Xu, C. Nat. Photon. 7, 33–37 (2013).

    CAS  Article  Google Scholar 

  15. Hung, Y. P., Albeck, J. G., Tantama, M. & Yellen, G. Cell Metab. 14, 545–554 (2011).

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

  1. Morgridge Institute for Research, Madison, WI, USA

    Alex J. Walsh, Joe T. Sharick & Melissa C. Skala

  2. Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA

    Melissa C. Skala

Authors
  1. Alex J. Walsh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joe T. Sharick
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Melissa C. Skala
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Melissa C. Skala.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Walsh, A.J., Sharick, J.T. & Skala, M.C. Imaging intratumoral metabolic heterogeneity. Nat Biomed Eng 3, 333–334 (2019). https://doi.org/10.1038/s41551-019-0398-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41551-019-0398-z

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing