Histochemistry and Cell Biology

, Volume 146, Issue 6, pp 695–707 | Cite as

Using electron microscopes to look into the lung

  • Matthias OchsEmail author
  • Lars Knudsen
  • Jan Hegermann
  • Christoph Wrede
  • Roman Grothausmann
  • Christian Mühlfeld


In the nineteenth century, there was a dispute about the existence of a lung alveolar epithelium which remained unsolved until the invention of electron microscopy (EM) and its application to the lung. From the early 1960s, Ewald Weibel became the master of lung EM. He showed that the alveolar epithelium is covered with a lining layer containing surfactant. Weibel also explained the phenomenon of “non-nucleated plates” observed already in 1881 by Albert Kölliker. Weibel’s most significant contribution was to the development of stereological methods. Therefore, quantitative characterization of lung structure revealing structure–function relationships became possible. Today, the spectrum of EM methods to study the fine structure of the lung has been extended significantly. Cryo-preparation techniques are available which are necessary for immunogold labeling of molecules. Energy-filtering techniques can be used for the detection of elements. There have also been major improvements in stereology, thus providing a very versatile toolbox for quantitative lung phenotype analyses. A new dimension was added by 3D EM techniques. Depending on the desired sample size and resolution, the spectrum ranges from array tomography via serial block face scanning EM and focused ion beam scanning EM to electron tomography. These 3D datasets provide new insights into lung ultrastructure. Biomedical EM is an ever-developing field. Its high resolution remains unparalleled. Moreover, EM has the unique advantage of providing an “open view” into cells and tissues within their full architectural context. Therefore, EM will remain an indispensable tool for a better understanding of the lung’s functional design.


Electron microscopy Volume EM Stereology Type II alveolar epithelial cell Surfactant Fibrosis Collapse induration 



Work from the authors’ laboratory was and is funded by the German Research Federation (DFG: OC23/7-3, 8-1, 9-3, 10-1; MU3118/2-1, KN916/1-1, SFB 587/TP B18; INST 192/504-1, INST 193/57-1; REBIRTH Cluster of Excellence), the Federal Ministry for Education and Research (BMBF: German Center for Lung Research DZL; 01DG14009) and the Swiss National Science Foundation (SNF: 116417, 121390, CRSII3_160704/1). The authors thank Dr. Hubert Schulz at the Training, Application and Support Center (TASC) of Carl Zeiss Microscopy, Oberkochen, Germany, for expert technical help with the FIB image acquisition and the generation of raw data sets at the Zeiss Application Center.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

Supplementary material 1 (AVI 22330 kb)

Supplementary material 2 (AVI 15774 kb)

Supplementary material 3 (AVI 21271 kb)

Supplementary material 4 (AVI 12837 kb)

Supplementary material 5 (AVI 16015 kb)

Supplementary material 6 (AVI 20565 kb)

Supplementary material 7 (AVI 5733 kb)

Supplementary material 8 (AVI 15413 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Matthias Ochs
    • 1
    • 2
    • 3
    Email author
  • Lars Knudsen
    • 1
    • 2
    • 3
  • Jan Hegermann
    • 1
    • 3
  • Christoph Wrede
    • 1
    • 3
  • Roman Grothausmann
    • 1
    • 3
  • Christian Mühlfeld
    • 1
    • 2
    • 3
  1. 1.Institute of Functional and Applied AnatomyHannover Medical SchoolHannoverGermany
  2. 2.Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH)Member of the German Center for Lung Research (DZL)HannoverGermany
  3. 3.REBIRTH Cluster of ExcellenceHannoverGermany

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