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Super resolution microscopy of living cells

Eukaryotic cells rely on specialized organelles to perform essential tasks, with each organelle exhibiting a unique architecture precisely adapted to its function. Among these, mitochondria and the endoplasmic reticulum (ER) play central roles in lipid synthesis, energy production, and the regulation of cellular metabolism. Our research aims to uncover how the architecture of these organelles is maintained and dynamically remodeled. A particular focus lies on contact sites—specialized membrane regions where two organelles closely interact to coordinate lipid metabolism and energy homeostasis.

We use live-cell super-resolution microscopy to visualize subcellular structures and organelle dynamics beyond the diffraction limit. By integrating advanced imaging techniques with biochemical and molecular approaches, we investigate the mechanisms that govern organelle communication and metabolic coordination.

Through this interdisciplinary approach, we aim to address fundamental questions in cell biology: How does organelle architecture emerge? What regulates ER–mitochondria interactions? And how do these processes shape lipid metabolism and support cellular adaptation?

For more information, visit our website

The image shows a section of a living human cancer cell in which the endoplasmic reticulum has been fluorescently labeled. The cell was imaged using Stimulated Emission Depletion (STED) super-resolution microscopy. The optical resolution enhancement reveals fine structural details that would remain hidden using conventional confocal laser scanning microscopy.

2024

Elancheliyan, P., Maruszczak, K. K., Serwa, R.A., Stephan, T., Gulgec, A. S., Borrero-Landazabal, M. A., Ngati S., Gosk, A., Jakobs, S., Wasilewski, M., Chacinska, A: "OCIAD1 and prohibitins regulate the stability of the TIM23 protein translocase".

Cell Reports 2024 Dec 24; 43(12):115038 (Article). 

2024

Scholz, J., Stephan, T., Pérez, A. G., Csiszár, A., Hersch, N., Fischer, L. S., Brühmann, S., Körber, S., Litschko, C., Mijanovic, L., Kaufmann, T., Lange, F., Springer, R., Pich, A., Jakobs, S., Peckham, M., Tarantola, M., Grashoff, C., Merkel, R., Faix, J.: "Decisive role of mDia-family formins in cell cortex function of highly adherent cells". 

Science Advances 2024 Nov;10(44):eadp5929 (Article).

2024

Stephan, T., Ilgen, P., Jakobs, S.: "Visualizing mitochondrial dynamics at the nanoscale"

Light Science & Applications (News and Views). 

2024

Chen, J., Stephan, T., Gaedke, F., Liu, T., Li, Y., Schauss, A., Chen, P., Wulff, V., Jakobs, S., Jüngst, C., Chen, Z.: "An aldehyde-crosslinking mitochondrial probe for STED imaging in fixed cells". 

Proceedings of the National Academy of Sciences 121, e2317703121 (Article).

2024

Stephan, T.*, Stoldt, S.*, Barbot, M.*, Carney, T.D., Lange, F., Bates, M., Bou Dib, P., Inamdar, K., Shcherbata, H.R., Meinecke, M., Riedel, D., Dennerlein, S., Rehling, P., Jakobs, S.: "Drosophila MIC10b can polymerize into cristae-shaping filaments"'. 

Life Science Alliance 7, e202302177 (Article). 

2023

Ebrahimi, V., Stephan, T., Kim, J., Carravilla, P., Eggeling, C., Jakobs, S., Han, K.Y.: "Deep learning enables fast, gentle STED microscopy". 

Communications Biology 6, 674 (Article). 

2022

Liu, T.*, Stephan, T.*, Chen, P., Keller-Findeisen, J., Chen, J., Riedel, D., Yang, Z., Jakobs, S., Chen, Z.: "Multi-color live-cell STED nanoscopy of mitochondria with a gentle inner membrane stain". 

Proceedings of the National Academy of Sciences 119, e2215799119 (Article). 

2022

Bates, M., Keller-Findeisen, J., Przybylski, A., Hüper, A., Stephan, T., Ilgen, P., Cereceda Delgado, A.R., D'Este, E., Egner, A., Jakobs, S., Sahl, S.J., Hell, S.W.: "Optimal precision and accuracy in 4Pi-STORM using dynamic spline PSF models". 

Nature Methods 19, 603–612 (Article). 

2020

Stephan, T.*, Brüser, C.*, Deckers, M., Steyer, A.M., Balzarotti, F., Barbot, M., Behr, T.S., Heim, G., Hübner, W., Ilgen, P., Lange, F., Pacheu-Grau, D., Pape, J.K., Stoldt, S., Huser, T., Hell, S.W., Möbius, W., Rehling, P., Riedel, D., Jakobs, S.: "MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation". 

The EMBO Journal 39, e104105 (Article). 

2020

Pape, J.K.*, Stephan, T.*, Balzarotti, F., Büchner, R., Lange, F., Riedel, D., Jakobs, S., Hell, S.W.: "Multicolor 3D MINFLUX nanoscopy of mitochondrial MICOS proteins". Proceedings of the National Academy of Sciences 117, 20607–20614 (Article). 

2020

Jakobs, S., Stephan, T., Ilgen, P., Brüser, C.: "Light Microscopy of Mitochondria at the Nanoscale". 

Annual Review of Biophysics (Review). 

2019

Stephan, T., Rösch, A., Riedel, D., Jakobs, S.: "Live-cell STED nanoscopy of mitochondrial cristae". 

Scientific Reports 9, 12419 (Article). 

2019

Stoldt, S.*, Stephan, T.*, Jans, D.C., Brüser, C., Lange, F., Keller-Findeisen, J., Riedel, D., Hell, S.W., Jakobs, S.: "Mic60 exhibits a coordinated clustered distribution along and across yeast and mammalian mitochondria". 

Proceedings of the National Academy of Sciences 116, 9853 (Article). 

*) These authors contributed equally.

Prof. Dr. Till Stephan
Buchmann Institute for Molecular Life Sciences

Goethe Universität Frankfurt am Main
Max-von-Laue-Straße 15

60438 Frankfurt am Main 

Building: N600
Office: Room 2.637
Lab: Room 2.613

T 0049 69 798 427 16
t.stephan@em.uni-frankfurt.de