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Putting Molecules in the Picture: Using Correlated Light Microscopy and Soft X-Ray Tomography to Study Cells

Synchrotron Light Sources and Free-Electron Lasers

Abstract

Transmission soft x-ray microscopy (SXM) is well suited to visualizing and quantifying mesoscale biology, that is to say structures ranging from the size of a typical molecular machine up to an intact cell. In SXM, the specimen is illuminated with “water window” soft x-rays (i.e., photons with energies in the range 284 e V to 543 e V). The degree to which the illumination is absorbed by a subcellular feature depends on its chemical composition. Carbon- and nitrogen-containing biomolecules strongly absorb the illumination, while water is relatively transparent. Similarities and differences in subcellular molecular content generate contrast in SXM images of the specimen without the use of stains. In this chapter, we discuss the basic concepts behind SXM and describe how 2D SXM data is used to calculate a 3D soft x-ray tomographic (SXT) reconstruction of the specimen. SXT offers significant advantages over other high-resolution cell imaging methods. A particular strength is the capacity to image intact, fully hydrated cells, including eukaryotes such as yeast or mammalian cells. In addition to stand-alone use, we will show that SXT data can be integrated into other imaging modalities to create a comprehensive view of the specimen. The combination of SXT with fluorescence data measured from the same specimen is particularly important, since this allows molecular localization data to be viewed directly in the context of the cell.

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Notes

  1. 1.

    https://www.excillum.com/

  2. 2.

    https://siriusxt.com/

  3. 3.

    https://www.energetiq.com/

  4. 4.

    FEI Software: https://www.fei.com/software/

  5. 5.

    https://www.zooniverse.org/projects/h-spiers/etch-a-cell

  6. 6.

    https://slidecam-camera.lbl.gov/

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Acknowledgements

This work was supported by the US Department of Energy, Office of Biological and Environmental Research (DE-AC02-05CH11231), the National Center for Research Resources of the National Institutes of Health (P41RR019664) and the National Institutes of General Medicine of the National Institutes of Health (P41GM103445), the Gordon and Betty Moore Foundation, and the Chan Zuckerberg Initiative. V.W. is supported by a German Research Foundation research fellowship WE 6221/1-1.

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Authors and Affiliations

  1. Department of Anatomy, University of California, San Francisco, CA, USA

    Axel Ekman, Jian-Hua Chen & Gerry McDermott

  2. Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    Venera Weinhardt

  3. Biomedical Sciences, University of California, San Diego, CA, USA

    Myan Do & Gerry McDermott

  4. Department of Anatomy, University of California, San Francisco, CA, USA

    Myan Do

  5. Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    Mark A. Le Gros & Carolyn A. Larabell

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  2. Zentrum für Synchrotronstrahlung, TU Dortmund, Dortmund, Germany

    Shaukat Khan

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    Jochen R. Schneider

  4. SLAC National Accelerator Laboratory Linac Coherent Light Source, Stanford University, Menlo Park, CA, USA

    Jerome B. Hastings

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Ekman, A. et al. (2019). Putting Molecules in the Picture: Using Correlated Light Microscopy and Soft X-Ray Tomography to Study Cells. In: Jaeschke, E., Khan, S., Schneider, J., Hastings, J. (eds) Synchrotron Light Sources and Free-Electron Lasers. Springer, Cham. https://doi.org/10.1007/978-3-319-04507-8_43-2

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    Putting Molecules in the Picture: Using Correlated Light Microscopy and Soft X-Ray Tomography to Study Cells
    Published:
    06 July 2019

    DOI: https://doi.org/10.1007/978-3-319-04507-8_43-3

  2. Putting Molecules in the Picture: Using Correlated Light Microscopy and Soft X-Ray Tomography to Study Cells
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    07 March 2019

    DOI: https://doi.org/10.1007/978-3-319-04507-8_43-2

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    Putting Molecules in the Picture: Using Correlated Light Microscopy and Soft X-ray Tomography to Study Cells
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    DOI: https://doi.org/10.1007/978-3-319-04507-8_43-1

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