Textlogo 'UFR', Abkürzung für 'Universität Freiburg'
Institut für Physikalische Chemie
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SingleMolecule

About us
News
The Group
The Research
Publications
Impressions
Teaching
Positions

Research group

Prof. Dr. Thorsten Hugel

Institute for Physical Chemistry

Albertstraße 21
79104 Freiburg

News

Group photo of all participants of the 10th Nanomanipulation Workshop in Aussois, France in 2026.

31.8.–02.09.2026

Group retreat in Todtmoos

Together with the group of Prof. Christine Selhuber-Unkel from University of Heidelberg we spent three days in the Black Forrest (Todtmoos, Sternenwarte) talking science and exchanging ideas. Plus, we got to see Saturn at the private observatory.

10/10, would recommend!

Team photo at the 2025 Husemann Cup.

23.07.2026

Husemann Cup

This years Husemann Cup will again be held in Buchenbach. Teams from the Faculty of Chemistry and Pharmacy, IMTEK and FMF will play in a hot match for the title. Afterwards, players and cheering people will enjoy the evening with cold drinks and a BBQ. We wish all teams a great match and tons of fun!

At the "Tag der Forschung" people are standing around an optical path trying to align the laser.

10.07.2026

Tag der Forschung

On Friday, 10.07.26, the annual „Tag der Forschung“ will take place. In case you have always wondered, which methods could be applied to measure single molecules or how to observe them, we got you covered. Come by out stand in the IPC area and we’ll have a chat.

The Group

Photo taken at the group excursion in August 2025 before a Rhein canoe tour.

Prof. Dr. Thorsten Hugel

Administration

Senior Scientists

Technical Staff

PhD Students and PostDocs

The Research

FRET

We want to obtain a real time picture of how components of a multi-protein complex interact to perform complex regulated tasks, in particular to see how a protein system might be more than the sum of its components. In living organisms many proteins work in complexes to form multi-component protein machines and to regulate cellular processes. The function of such multi-component machines is usually addressed by dividing them into a collection of two state systems at equilibrium. Many molecular machines, like e.g. the heat shock protein Hsp90, work in large complexes with multiple states out of equilibrium by utilizing the energy of ATP hydrolysis.

These studies impact the understanding of the Hsp90 machinery as well as general principles of multi-component protein systems, which is the basis for understanding cellular processes.

AFM

Polymers at interfaces play an important role in (bio)technology, but a fundamental understanding of their interaction is still lacking. We develop AFM-based methods to probe single polymer adhesion and friction at interfaces. Experiments of this kind will help in gaining a fundamental understanding of adhesion and friction properties of multi-component systems. Furthermore, we extend our methods to analyze the mechanics of adaptive material systems, the charge separation properties of triboelectric materials and the elasticity and structure of cartilage for the understanding of osteoarthritis.

Publications of the Hugel group

Thorsten Hugel

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Es werden Publikation(en) von 2016 bis 2026 angezeigt

  • Zhang, Y., Grundmann, L., Vollmar, L., Schimpf, J., Hübscher, V., Areeb, M., Grishkovskaya, I., Moddemann, A., Werner, K., Hugel, T., Haselbach, D., & Rospert, S. (2026). The cotranslational cycle of the ribosome-bound Hsp70 homolog Ssb. Nature Communications, 17(1), 961. https://doi.org/10.1038/s41467-025-67685-6
  • Anandamurugan, A., Eidloth, A., Frank, V., Wortmann, P., Schrangl, L., Lan, C., Schütz, G. J., & Hugel, T. (2026). Single-molecule FRET and tracking of transfected biomolecules in living cells. Biophysical Journal, 125(12), 3025–3033. https://doi.org/10.1016/j.bpj.2025.09.024
  • Huang, D., Hugel, T., Balzer, B. N., & Reiter, G. (2025). Temperature dependence of crystal melt coexistence for supported polyethylene filaments. Nature Communications, 16(1). https://doi.org/10.1038/s41467-025-67465-2
  • Bhuiyan, T., Arecco, N., Mendoza Sanchez, P. K., Kim, J., Schwan, C., Weyrauch, S., Nizamuddin, S., Prunotto, A., Tekman, M., Biniossek, M. L., Knapp, B., Koidl, S., Drepper, F., Huesgen, P. F., Grosse, R., Hugel, T., & Arnold, S. J. (2025). TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing factors. Cell Reports, 44(5), 115616. https://doi.org/10.1016/j.celrep.2025.115616
  • Götz, M., Hugel, T., Schimpf, J., Vollmar, L., & Schmid, S. (2024). Reply to: On the statistical foundation of a recent single molecule FRET benchmark. Nature Communications, 15(1), 3626. https://doi.org/10.1038/s41467-024-47734-2
  • Vollmar, L., Bebon, R., Schimpf, J., Flietel, B., Celiksoy, S., Sönnichsen, C., Godec, A., & Hugel, T. (2024). Model-free inference of memory in conformational dynamics of a multi-domain protein. Journal of Physics A: Mathematical and Theoretical, 57(36), 365001. https://doi.org/10.1088/1751-8121/ad6d1e
  • Tancredi, R., Feltrin, A., Infirri, G. S., Toso, S., Vollmar, L., Hugel, T., & Baiesi, M. (2024). Constrained hidden Markov models reveal further Hsp90 protein states. New Journal of Physics, 26(7), 073023. https://doi.org/10.1088/1367-2630/ad5def
  • Hugel, T. (2024). New dimensions for fluorescence-based barcoding in complex mixtures. Nature Nanotechnology, 19(8), 1081–1082. https://doi.org/10.1038/s41565-024-01686-2
  • Huang, D., Hugel, T., & Reiter, G. (2024). Mechanism for the formation of millimeter-long solid filaments by spin coating dilute solutions of a crystallizable polymer. Macromolecules, 57(8), 3696–3705. https://doi.org/10.1021/acs.macromol.3c02524
  • Vollmar, L., Schimpf, J., Hermann, B., & Hugel, T. (2024). Cochaperones convey the energy of ATP hydrolysis for directional action of Hsp90. Nature Communications, 15(1), 569. https://doi.org/10.1038/s41467-024-44847-6
  • Mondol, T., Hugel, T., & Sohmen, B. (2023). Single molecule fluorescence methods for molecular chaperones and their client interactions. In Biophysics of molecular chaperones : function, mechanisms and client protein interactions (pp. 181–198). Royal Society of Chemistry. https://doi.org/10.1039/bk9781839165986-00181
  • Mondol, T., Silbermann, L.-M., Schimpf, J., Vollmar, L., Hermann, B., Tych, K., & Hugel, T. (2023). Aha1 regulates Hsp90’s conformation and function in a stoichiometry-dependent way. Biophysical Journal, 122(17), 3458–3468. https://doi.org/10.1016/j.bpj.2023.07.020
  • Sohmen, B., Beck, C., Frank, V., Seydel, T., Hoffmann, I., Hermann, B., Nüesch, M., Grimaldo, M., Schreiber, F., Wolf, S., Roosen-Runge, F., & Hugel, T. (2023). The onset of molecule‐spanning dynamics in heat shock protein Hsp90. Advanced Science, 10(36), 2304262. https://doi.org/10.1002/advs.202304262
  • Zitation nicht verfügbar
  • Dai, K., Pol, M. D., Saile, L., Sharma, A., Liu, B., Thomann, R., Trefs, J. L., Qiu, D., Moser, S., Wiesler, S., Balzer, B. N., Hugel, T., Jessen, H., & Pappas, C. G. (2023a). Spontaneous and selective peptide elongation in water driven by aminoacyl phosphate esters and phase changes. Journal of the American Chemical Society, 145(48), 26086–26094. https://doi.org/10.1021/jacs.3c07918
  • Dai, K., Pol, M. D., Saile, L., Sharma, A., Liu, B., Thomann, R., Trefs, J. L., Qiu, D., Moser, S., Wiesler, S., Balzer, B. N., Hugel, T., Jessen, H., & Pappas, C. G. (2023). Systems chemistry of aminoacyl phosphates: Spontaneous and selective peptide oligomerisation in water driven by phase changes. https://doi.org/10.26434/chemrxiv-2023-lg3cw
  • Lan, C., Kim, J., Ulferts, S., Aprile-Garcia, F., Weyrauch, S., Anandamurugan, A., Grosse, R., Sawarkar, R., Reinhardt, A., & Hugel, T. (2023). Quantitative real-time in-cell imaging reveals heterogeneous clusters of proteins prior to condensation. Nature Communications, 14(1), 4831. https://doi.org/10.1038/s41467-023-40540-2
  • Cai, W., Jäger, M., Bullerjahn, J. T., Hugel, T., Wolf, S., & Balzer, B. N. (2023). Anisotropic friction in a ligand-protein complex. Nano Letters, 23(10), 4111–4119. https://doi.org/10.1021/acs.nanolett.2c04632
  • Agam, G., Hugel, T., Thurn, J., Barth, A., Seidel, C. A. M., Lamb, Don. C., & Cordes, T. (2023). Reliability and accuracy of single-molecule FRET studies for characterization of structural dynamics and distances in proteins. Nature Methods, 20(4), 523–535. https://doi.org/10.1038/s41592-023-01807-0
  • Götz, M., Hugel, T., Vollmar, L., & Schmid, S. (2022). A blind benchmark of analysis tools to infer kinetic rate constants from single-molecule FRET trajectories. Nature Communications, 13(1), 5402. https://doi.org/10.1038/s41467-022-33023-3
  • Cai, W., Trefs, J. L., Hugel, T., & Balzer, B. N. (2022). Anisotropy of [pi]–[pi] stacking as basis for superlubricity. ACS Materials Letters, 172–179. https://doi.org/10.1021/acsmaterialslett.2c00974
  • Cai, W., Bullerjahn, J. T., Lallemang, M., Kroy, K., Balzer, B. N., & Hugel, T. (2022). Angle-dependent strength of a single chemical bond by stereographic force spectroscopy. Chemical Science, 13(19), 5734–5740. https://doi.org/10.1039/D2SC01077A
  • Tschaikowsky, M., Brander, S., Barth, V., Thomann, R., Rolauffs, B., Balzer, B. N., & Hugel, T. (2022). The articular cartilage surface is impaired by a loss of thick collagen fibers and formation of type I collagen in early osteoarthritis. Acta Biomaterialia, 146, 274–283. https://doi.org/10.1016/j.actbio.2022.04.036
  • Lallemang, M., Yu, L., Cai, W., Rischka, K., Hartwig, A., Haag, R., Hugel, T., & Balzer, B. N. (2022). Multivalent non-covalent interactions lead to strongest polymer adhesion. Nanoscale, 14(10), 3768–3776. https://doi.org/10.1039/D1NR08338D
  • Lohner, P. S., Zmyslia, M., Thurn, J., Pape, J. K., Gerasimaite, R., Keller-Findeisen, J., Gröer, S., Deuringer, B. B., Süss, R., Walther, A., Hell, S. W., Lukinavicius, G., Hugel, T., & Jessen-Trefzer, C. (2021). Inside a shell — organometallic catalysis inside encapsulin nanoreactors. Angewandte Chemie, 133(44), 24028–24034. https://doi.org/10.1002/ange.202110327
  • Lan, C., Rawat, P., Sawarkar, R., & Hugel, T. (2021). Quantification of the onset of condensation in negative elongation factors. Biophysical Journal, 120(3), 29a. https://doi.org/10.1016/j.bpj.2020.11.434
  • Hugel, T., Schmid, S., Wolf, S., Hellenkamp, B., Sohmen, B., Thurn, J., & Stock, G. (2021). Combining single-molecule fluorescence and MD-simulations to delineate the kinetics and regulation of proteins. Biophysical Journal, 120(3), 100a–101a. https://doi.org/10.1016/j.bpj.2020.11.823
  • Anandamurugan, A., Wortmann, P., Lan, C., Garcia Fernando, A., Veil, M., Schrangl, L., Sawarkar, R., Driever, W., Schütz, G. J., & Hugel, T. (2021). Protein conformational dynamics in cellula and IN VIVO using live-cell single-molecule fret hilo microscopy. Biophysical Journal, 120(3), 114a. https://doi.org/10.1016/j.bpj.2020.11.2272
  • Lerner, E., Barth, A., Hendrix, J., Hugel, T., & Weiss, S. (2021). FRET-based dynamic structural biology: Challenges, perspectives and an appeal for open-science practices. eLife, 10, Supporting Information. https://doi.org/10.7554/elife.60416
  • Wang, H., Lallemang, M., Hermann, B., Wallin, C., Loch, R., Blanc, A., Balzer, B. N., Hugel, T., & Luo, J. (2021). ATP impedes the inhibitory effect of Hsp90 on A[beta]40 fibrillation. Journal of Molecular Biology, 433(2), 166717. https://doi.org/10.1016/j.jmb.2020.11.016
  • Sousa Machado, J. N. de, Vollmar, L., Schimpf, J., Chaudhury, P., Kumariya, R., Does, C. van der, Hugel, T., & Albers, S. V. (2021). Autophosphorylation of the KaiC‐like protein ArlH inhibits oligomerization and interaction with ArlI, the motor ATPase of the archaellum. Molecular Microbiology, 116(3), 943–956. https://doi.org/10.1111/mmi.14781
  • Lohner, P. S., Zmyslia, M., Thurn, J., Pape, J. K., Gerasimaite, R., Keller-Findeisen, J., Gröer, S., Deuringer, B. B., Süss, R., Hell, S. W., Lukinavicius, G., Hugel, T., & Jessen-Trefzer, C. (2021). Inside a shell – organometallic catalysis inside Encapsulin nanoreactors. Angewandte Chemie. International Edition, 60(44), 23835–23841. https://doi.org/10.1002/anie.202110327
  • Tschaikowsky, M., Neumann, T., Brander, S., Haschke, H., Rolauffs, B., Balzer, B. N., & Hugel, T. (2021). Hybrid fluorescence-AFM explores articular surface degeneration in early osteoarthritis across length scales. Acta Biomaterialia, 126, 315–325. https://doi.org/10.1016/j.actbio.2021.03.034
  • Wolf, S., Sohmen, B., Hellenkamp, B., Thurn, J., Stock, G., & Hugel, T. (2021). Hierarchical dynamics in allostery following ATP hydrolysis monitored by single molecule FRET measurements and MD simulations. Chemical Science, 12(9), 3350–3359. https://doi.org/10.1039/d0sc06134d
  • Tschaikowsky, M., Selig, M., Brander, S., Balzer, B. N., Hugel, T., & Rolauffs, B. (2021). Proof-of-concept for the detection of early osteoarthritis pathology by clinically applicable endomicroscopy and quantitative AI-supported optical biopsy. Osteoarthritis and Cartilage, 29(2), 269–279. https://doi.org/10.1016/j.joca.2020.10.003
  • Lerner, E., Hugel, T., & Weiss, S. (2020). The FRET-based structural dynamics challenge – community contributions to consistent and open science practices. arXiv. https://doi.org/10.48550/arxiv.2006.03091
  • Schmid, S., & Hugel, T. (2020). Controlling protein function by fine-tuning conformational flexibility. eLife, 9, e57180. https://doi.org/10.7554/elife.57180
  • Kolberg, A., Wenzel, C., Hugel, T., Gallei, M., & Balzer, B. N. (2020). Covalent attachment of single molecules for AFM-based force spectroscopy. Journal of Visualized Experiments. Chemistry, 157, e60934. https://doi.org/10.3791/60934
  • Wolf, S., Sohmen, B., Hellenkamp, B., Hugel, T., & Stock, G. (2019a). Identification of metastable conformational states of protein dynamics.
  • Wolf, S., Sohmen, B., Hellenkamp, B., Hugel, T., & Stock, G. (2019b). Protein-ligand interaction and hierarchical complex dynamics of Hsp90.
  • Schmid, S., & Hugel, T. (2019). Same equilibrium. Different kinetics. Protein functional consequences. https://doi.org/10.1101/838938
  • Tschaikowsky, M., Brander, S., Balzer, B. N., Rolauffs, B., & Hugel, T. (2019). Proof-of-concept for the detection of early osteoarthritis pathology by endomicroscopy. https://doi.org/10.1101/734368
  • Kolberg, A., Wenzel, C., Hackenstrass, K., Schwarzl, R., Rüttiger, C., Hugel, T., Gallei, M., Netz, R. R., & Balzer, B. N. (2019). Opposing temperature dependence of the stretching response of single peg and pnipam polymers. Journal of the American Chemical Society, 141(29), 11603–11613. https://doi.org/10.1021/jacs.9b04383
  • Brander, S., Jank, T., & Hugel, T. (2019). AFM imaging suggests receptor – free penetration of lipid bilayers by toxins. Langmuir, 35(2), 365–371. https://doi.org/10.1021/acs.langmuir.8b03146
  • Jahn, M., Tych, K. M., Girstmair, H., Steinmaßl, M., Hugel, T., Buchner, J., & Rief, M. (2018). Folding and domain interactions of three orthologs of Hsp90 studied by single-molecule force spectroscopy. Structure, 26(1), 96–105.e4. https://doi.org/10.1016/j.str.2017.11.023
  • Ye, W., Götz, M., Celiksoy, S., Tüting, L., Ratzke, C., Prasad, J., Ricken, J., Wegner, S. V., Ahijado-Guzmán, R., Hugel, T., & Sönnichsen, C. (2018). Conformational dynamics of a single protein monitored for 24 h at video rate. Nano Letters, 18(10), 6633–6637. https://doi.org/10.1021/acs.nanolett.8b03342
  • Tych, K. M., Jahn, M., Gegenfurtner, F., Hechtl, V. K., Buchner, J., Hugel, T., & Rief, M. (2018). Nucleotide-dependent dimer association and dissociation of the chaperone Hsp90. The Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces & Biophysical, 122(49), 11373–11380. https://doi.org/10.1021/acs.jpcb.8b07301
  • Hellenkamp, B., Thurn, J., Stadlmeier, M., & Hugel, T. (2018). Kinetics of transient protein complexes determined via diffusion-independent microfluidic mixing and fluorescence stoichiometry. The Journal of Physical Chemistry B, 122(49), 11554–11560. https://doi.org/10.1021/acs.jpcb.8b07437
  • Götz, M., Wortmann, P., Schmid, S., & Hugel, T. (2018). Using three-color single-molecule FRET to study the correlation of protein interactions. JoVE. Video Journal, (131). https://doi.org/10.3791/56896
  • Schmid, S., & Hugel, T. (2018). Efficient use of single molecule time traces to resolve kinetic rates, models and uncertainties. The Journal of Chemical Physics, 148, 123312. https://doi.org/10.1063/1.5006604
  • Schmid, S., Götz, M., & Hugel, T. (2018). Effects of inhibitors on Hsp90′s conformational dynamics, cochaperone and client interactions. ChemPhysChem, 19(14), 1716–1721. https://doi.org/10.1002/cphc.201800342
  • Hellenkamp, B., Schmid, S., & Hugel, T. (2018). Precision and accuracy of single-molecule FRET measurements – a multi-laboratory benchmark study. Nature Methods, 15(9), 669–676. https://doi.org/10.1038/s41592-018-0085-0
  • Wortmann, P., Götz, M., & Hugel, T. (2017). Cooperative nucleotide binding in Hsp90 and its regulation by Aha1. Biophysical Journal, 113(8), 1711–1718. https://doi.org/10.1016/j.bpj.2017.08.032
  • Liese, S., Gensler, M., Krysiak, S., Schwarzl, R., Achazi, A., Paulus, B., Hugel, T., Rabe, J. P., & Netz, R. R. (2017). Hydration effects turn a highly stretched polymer from an entropic into an energetic spring. ACS Nano, 11(1), 702–712. https://doi.org/10.1021/acsnano.6b07071
  • Hellenkamp, B., Wortmann, P., Kandzia, F., Zacharias, M., & Hugel, T. (2017). Multidomain structure and correlated dynamics determined by self-consistent FRET networks. Nature Methods, 14(2), 174–180. https://doi.org/10.1038/NMETH.4081
  • Boettcher, K., Kienle, S., Nachtsheim, J., Burgkart, R., Hugel, T., & Lieleg, O. (2016). The structure and mechanical properties of articular cartilage are highly resilient towards transient dehydration. Acta Biomaterialia, 29, 180–187. https://doi.org/10.1016/j.actbio.2015.09.034
  • Götz, M., Wortmann, P., Schmid, S., & Hugel, T. (2016). A Multicolor Single-Molecule FRET Approach to Study Protein Dynamics and Interactions Simultaneously. In Single-Molecule Enzymology: Fluorescence-Based and High-Throughput Methods (pp. 487–516). Elsevier. https://doi.org/10.1016/bs.mie.2016.08.024
  • Schmid, S., Götz, M., & Hugel, T. (2016). Single-molecule analysis beyond dwell times : demonstration and assessment in and out of equilibrium. Biophysical Journal, 111(7), 1375–1384. https://doi.org/10.1016/j.bpj.2016.08.023
  • Schwierz, N., Krysiak, S., Hugel, T., & Zacharias, M. (2016). Mechanism of reversible peptide–bilayer attachment : combined simulation and experimental single-molecule study. Langmuir, 32(3), 810–821. https://doi.org/10.1021/acs.langmuir.5b03435
  • Balzer, B. N., & Hugel, T. (2016). Single-molecule detection and manipulation. Reference Module in Materials Science and Materials Engineering, 1–19.
  • Jahn, M., Buchner, J., Hugel, T., & Rief, M. (2016). Folding and assembly of the large molecular machine Hsp90 studied in single-molecule experiments. Proceedings of the National Academy of Sciences of the United States of America, 113(5), 1232–1237. https://doi.org/10.1073/pnas.1518827113

Impressions

Lesley Göbel, Sekretärin Prof. Hugel

Study Programmes

Physical chemistry, owing to its close connection to physics, has traditionally been the most interdisciplinary of the core disciplines in the study of chemistry. As a foundational subject, it plays a particularly important role in teaching, providing students with essential experimental methods and theoretical concepts.

Our curriculum offers both undergraduate (B.Sc.) and graduate-level (M.Sc. and Ph.D.) students intensive practical and theoretical training in the latest concepts, methods, and applications of physical and theoretical chemistry.

Find out more about our study programmes here

Positions

PhD-, Bachelor- and Master theses

We regularly provide exciting and current research topics for Bachelor’s, Master’s, and doctoral theses.
Interested? Please submit your application directly to Prof. Dr. Thorsten Hugel!

Hiwi-Stellen

Teaching assistant positions for laboratory courses and/or exercises are available every semester.
Interested? Please submit your application directly to Lesley Göbel!