Prof. Dr. Carsten Grashoff
Exploring Cellular Mechanics on Molecular Scales
Biophysics
Cell Biology/Molecular Biology
Cell Mechanics
We are interested in the mechanobiology of cells, particularly the molecular mechanisms underlying cellular force transduction processes during cell adhesion. To investigate this, we have developed single-molecule calibrated FRET-based biosensors able to monitor mechanical forces of just a few piconewton in cells. Application of these genetically encoded tension sensors to molecules that mediate cell-matrix and cell-cell adhesion enables the quantification of cell adhesion processes in living cells using fluorescence lifetime microscopy (FLIM). The combination with single-excitation wavelength, dual colour FLIM allows the simultaneous analysis of two biosensors and thus the investigation of multiple force transducing structures in parallel. We use these technologies to investigate various intracellular processes of mechanotransduction that have been inaccessible to other techniques but play an important role for distinct patho-physiological processes.
Vita
- 1997-2001: Student of Applied Science, University of Freiberg, Germany
- 2001-2002: Diploma Student, Robert Koch Institute, Berlin, Germany
- 2003: Georgius Agricola Medal, University of Freiberg, Germany
- 2002-2007: PhD Student, Max Planck Institute of Biochemistry, Munich, Germany
- 2007-2010: Postdoctoral Researcher, University of Virginia, Charlottesville, USA
- 2011-2014: Emmy Noether Research Group Leader, Max Planck Institute of Biochemistry, Munich, Germany
- 2014: Leopoldina Early Career Award, German National Academy of Sciences
- 2014-2018: Max Planck Research Group Leader, Max Planck Institute of Biochemistry, Munich, Germany
- 2018: W2 Professor, University of Münster, Germany
- 2018: Binder Innovation Prize, German Society for Cell Biology
- Since 2023: W3 Professor, University of Münster, Germany
Selected references
Sadhanasatish T, Augustin K, Windgasse L, Chrostek-Grashoff A, Rief M, Grashoff, C. A molecular optomechanics approach reveals functional relevance of force transduction across talin and desmoplakin. Science Advances 9, eadg3347; 10.1126/sciadv.adg3347 (2023).
Fischer LS, Klingner C, Schlichthaerle T, Strauss MT, Böttcher R, Fässler R, Jungmann R, Grashoff, C. Quantitative single-protein imaging reveals molecular complex formation of integrin, talin, and kindlin during cell adhesion. Nature Communications 12, 919; 10.1038/s41467-021-21142-2 (2021).
Kanoldt V, Kluger C, Barz C, Schweizer AL, Ramanujam D, Windgasse L, Engelhardt S, Chrostek-Grashoff A, Grashoff C. Metavinculin modulates force transduction in cell adhesion sites. Nature Communications 11, 6403; 10.1038/s41467-020-20125-z (2020).
Ringer P, Weißl A, Cost AL, Freikamp A, Sabass B, Mehlich A, Tramier M, Rief M, Grashoff C. Multiplexing molecular tension sensors reveals piconewton force gradient across talin-1. Nature Methods 14, 1090–1096; 10.1038/nmeth.4431 (2017).
Austen K, Ringer P, Mehlich A, Chrostek-Grashoff A, Kluger C, Klingner C, Sabass B, Zent R, Rief M, Grashoff, C. Extracellular rigidity sensing by talin isoform-specific mechanical linkages. Nature Cell Biology 17, 1597–1606; 10.1038/ncb3268 (2015).
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