© Raphael Schleutker

Research Topic

We are interested in the molecular processes underlying mechanical force transmission in cells. To investigate the underlying principles, we develop microscopy techniques that allow us to quantify mechanical forces acting across individual molecules with piconewton-sensitivity in living cells. Our most prominent method is based upon Fӧrster resonance energy transfer (FRET)–based biosensors, in which two fluorophores are connected by a mechanosensitive linker peptide that elongates in response to mechanical tension. Peptide extension leads to a decrease in FRET efficiency, which can be quantified with fluorescence lifetime microscopy (FLIM). By inserting these tension sensors into proteins of interest, mechanical tension across the respective target protein can be quantified. We have applied this method to study molecular forces across cell adhesion proteins like vinculin, talin and desmoplakin and have also developed tools to insert these biosensors genomically into LINC complex proteins. We complement these approaches with an optogenetic approach called Molecular Optomechanics, which allows the modulation of force transmission across distinct molecular linkages in cells. Together, these experiments can reveal if, where and when distinct molecules experience mechanical tension in cells, and they demonstrate how relevant these processes are for a given mechanobiological process.

Selected Publications

  • Rangarajan, S., Espeter, L., Drexler, H.C.A., Chrostek-Grashoff, A., Grashoff, C. (2025). Talin force coupling underlies eukaryotic cell-substrate adhesion. Nat Communications (in press). doi: 10.1038/s41467-025-67354-8.

  • Windgasse, L., Grashoff, C. (2025). A conformational change in α-catenin's actin-binding domain governs adherens junction maturation. Communications Biology. 8(1):1325. doi: 10.1038/s42003-025-08785-3.

  • Sadhanasatish T., Augustin K., Windgasse L., Chrostek-Grashoff A., Rief M., Grashoff C. (2023). A molecular optomechanics approach reveals functional relevance of force transduction across talin and desmoplakin. Science Advances, 23;9(25):eadg3347. doi: 10.1126/sciadv.adg3347.

  • Fischer, L. S., Klingner, C., Schlichthaerle, T., Strauss, M. T., Böttcher, R., Fässler, R., Jungmann, R. & Grashoff, C. (2021). Quantitative single-protein imaging reveals molecular complex formation of integrin, talin, and kindlin during cell adhesion. Nature Communications 12, 919; doi: 10.1038/s41467-021-21142-2.

  • Fischer L.S., Rangarajan S., Sadhanasatish T., Grashoff C. (2021). Molecular Force Measurement with Tension Sensors. Annual Reviews of Biophysics, 50:595-616. doi: 10.1146/annurev-biophys-101920-064756.