Abstract
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Title:
Correlative fluorescence microscopy, transmission electron microscopy and
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secondary ion mass spectrometry (CLEM-SIMS) for cellular imaging
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Felix Lange
1,2,
¶
, Paola Agüi-Gonzalez
3,4,
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, Dietmar Riedel
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, Nhu T.N. Phan
3,4
, Stefan Jakobs
1,2,4,&
,
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Silvio O. Rizzoli
3,4,&
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1
Research Group Mitochondrial Structure and Dynamics, Max Planck Institute for Biophysical
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Chemistry, Göttingen, Germany
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2
Clinic for Neurology, University Medical Center Göttingen, Germany
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3
Department of Neuro- and Sensory Physiology, University Medical Center Göttingen, Germany
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4
Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen,
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Germany
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5
Laboratory of Electron Microscopy, Max Planck Institute for Biophysical Chemistry, Göttingen,
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Germany
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¶
These authors contributed equally to this work.
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&
These authors also contributed equally to this work.
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*
Correspondence to: sjakobs@gwdg.de; srizzol@gwdg.de
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Abstract
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Electron microscopy (EM) has been employed for decades to analyze cell structure. To also
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analyze the positions and functions of specific proteins, one typically relies on immuno-EM or on
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a correlation with fluorescence microscopy, in the form of correlated light and electron microscopy
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(CLEM). Nevertheless, neither of these procedures is able to also address the isotopic
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composition of cells. To solve this, a correlation with secondary ion mass spectrometry (SIMS)
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would be necessary. SIMS has been correlated in the past to EM or to fluorescence microscopy
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in biological samples, but not to CLEM. We achieved this here, using a protocol based on
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transmission EM, conventional epifluorescence microscopy and nanoSIMS. The protocol is easily
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applied, and enables the use of all three technologies at high performance parameters. We
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suggest that CLEM-SIMS will provide substantial information that is currently beyond the scope of
