Scientific Curriculum
• Studies of Applied Science, Technical Universitz of Freiberg (1997-2001)
• PhD studies at the Max-Planck-Institute of Biochemistry (2002 - 2007)
• Postdoctoral studies at the University of Virginia, USA (2007 – 2010)
• Emmy Noether Research Group Leader at the Max-Planck-Institute of Biochemistry (2011 - 2014)
• Max Planck Research Group Leader at the Max-Planck-Institute of Biochemistry (2014 - 2017)
• Professor of Quantitative Cell Biology an der WWU Münster (since 2018)


Teaching
Cell Biology
Current Research Focus
• Cell Biology
• Mechanobiology
• Molecular Cell Adhesion Mechanics


Four Selected Research Articles
1. Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M, Yang MT, McLean MA, Sligar SG, Chen CS, Ha T, and Schwartz MA (2010). Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 466: 263-266.
https://www.nature.com/articles/nature09198
2. Austen KA, Ringer P, Mehlich A, Chrostek-Grashoff A, Kluger C, Klingner C, Sabass B, Zent R, Rief M, and Grashoff C (2015). Extracellular rigidity sensing by talin isoform-specific mechanical linkages. Nat Cell Biol 17: 1597-1606.
https://www.nature.com/articles/ncb3268
3. Ringer P, Weißl A, Cost AL, Freikamp A, Sabass B, Mehlich A, Tramier M, Rief M and Grashoff C (2017). Multiplexing molecular tension sensors reveals piconewton force gradient across talin-1. Nat Methods 14: 1090-1096.
https://www.nature.com/articles/nmeth.4431
4. Price AJ, Cost AL, Ungewiβ H, Waschke J, Dunn AR, and Grashoff C. 2018. Nat Commun 11; 9:5284.
https://www.nature.com/articles/s41467-018-07523-0


Four Selected Review Articles
1. Hoffman BD, Grashoff C, and Schwartz MA (2011). Dynamic molecular processes mediate cellular mechanotransduction. Nature 475: 316-323.
https://www.nature.com/articles/nature10316
2. Freikamp A, Cost AL and Grashoff C. (2016). The Piconewton Force Awakens: Quantifying Mechanics in Cells. Trends Cell Biol 26 (11): 838-847.
https://www.sciencedirect.com/science/article/pii/S0962892416300988
3. Ringer P, Colo G, Fässler R, and Grashoff C. (2017). Sensing the mechano-chemical properties of the extracellular matrix. Unforgettable force - crosstalk and memory of mechanosensitive structures. Matrix Biol 64: 6-16.
https://www.sciencedirect.com/science/article/pii/S0945053X1730018
4. Kanoldt, V, Fischer SL, Grashoff C. (2018). Unforgettable force - crosstalk and memory of mechanosensitive structures. Biol Chem, Dec 20.
https://doi.org/10.1515/hsz-2018-0328


Four Selected Method Articles
1. Austen K, Kluger C, Freikamp A, Chrostek-Grashoff A and Grashoff C. (2013). Generation and analysis of biosensors to measure mechanical forces within cells. Methods Mol Biol 1066: 169-184.
https://link.springer.com/protocol/10.1007%2F978-1-62703-604-7_15
2. Freikamp A, Mehlich A, Klingner C and Grashoff C. (2016). Investigating piconewton forces in cells by FRET-based molecular force microscopy. J Struct Biol 197 (1): 37-42.
https://www.sciencedirect.com/science/article/pii/S1047847716300478
3. Cost AL, Ringer P, Chrostek-Grashoff A and Grashoff C. (2015). How to Measure Molecular Forces in Cells: A Guide to Evaluating Genetically-Encoded FRET-Based Tension Sensors. Cell Mol Bioeng 8(1):96-105.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361753/
4. Cost AL, Khalaji S, and Grashoff C. (2019). Genetically Encoded FRET-Based Tension Sensors. Curr Protoc Cell Biol. Mar 13:e85.
https://currentprotocols.onlinelibrary.wiley.com/doi/abs/10.1002/cpcb.85

Our Research in the News
Eisenstein. (2017). A Measure of Molecular Muscle. Nature 12: 255-257.
https://www.nature.com/articles/544255a
Vogt N. (2016). Sensing some tension. Nat Methods 13: 17.
https://www.nature.com/articles/nmeth.3726
De Souza N. (2014). Tiny tools to measure force. Nat Methods 11:29.
https://www.nature.com/articles/nmeth.2778

Research Summary
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.

Selected Projects
• Cell adhesion mechanics of collective cell migration (SFB863)
• Mechanical loading of desmosomes (SPP1782)
• Integrin-subtype specific force transduction (SFB1348)
• Nanoscale-organisation of integrin-based adhesions (DFG-ANR)
• Mechanobiology of Adipocytes (HFSP)

Publications

  • Kanoldt V, Fischer L, Grashoff C. . ‘Unforgettable force – crosstalk and memory of mechanosensitive structures.’ Biological Chemistry Band 400, Heft 6. doi: 10.1515/hsz-2018-0328.
  • Price AJ, Cost AL, Ungewiß H, Waschke J, Dunn AR, Grashoff C. . ‘Mechanical loading of desmosomes depends on the magnitude and orientation of external stress.’ Nature Communications 9. doi: 10.1038/s41467-018-07523-0.