Cell Mechanics

Mechanical properties of cells are very often connected to their state and function. They can thus serve as an intrinsic biophysical marker of cell state transitions, such as metastasis of cancer cells, activation of leukocytes, or progression through the cell cycle. To characterize those mechanical properties we have at our disposal a unique panel of methods that includes atomic force microscopy (AFM), real-time deformability cytometry (RT-DC) and optical stretcher, – the latter two developed by the Guck lab. These techniques can operate at measurement rates of up to 1000 cells per second and at timescales from milliseconds to minutes, which allows for accessing different biologically relevant regimes.
These tools are used to compare mechanical properties of different cell populations, or to find mechanical subpopulations within heterogeneous samples. Our work with the optical stretcher has shown that metastatic cancer cells are more compliant than their non-invasive counterparts [1]. This differential mechanical behavior correlated with a reduced F-actin content in malignant cells. The lab has also significantly contributed to understanding the mechanical properties of cells forming nervous tissue with the finding that Müller glial cells (previously considered to have scaffolding function for nervous cells) are actually more compliant than neurons [2]. Another example of the work of our lab shows that timescale dependence of physical properties can be linked to the cell’s biological function as shown for different cell types of the myeloid lineage [3]. Circulating blood cells are elastically compliant on short time-scales, required for quick advection through microcapillary constrictions, while migrating immune cells have low viscosity on long timescales for easy flowing through tissue gaps. Deviation from the normal mechanical phenotype of blood cells is now being used to diagnose blood-related disorders.
Besides mechanical phenotyping of the central nervous system, hematopoietic system and cancer cells, we are currently interested in stem cell differentiation in the context of adipogenesis, embryonic stem cell differentiation as well as reprogramming of somatic cells into induced pluripotent stem cells (iPSC). We further study the role of mechanics during cell cycle progression with special emphasis on mitosis.
The objective of our studies is not only to compare the cells’ biophysical properties, but also to understand the mechanisms underpinning those differences and their relation to the biological function of the cell. To identify the main structural and signaling contributors to the mechanical phenotypes of cells we are using molecular biology, imaging, biomimetic engineering and machine learning techniques that allow us to get a birds-eye view on regulation of cell physical properties.

Cell mechanics is a powerful tool that can be used to characterize cells, to monitor their mechanical behavior during differentiation processes, and to diagnose pathological alterations. Due to its success in basic research, the mechanical analysis of cells promises to be a simple and efficient approach, particularly with regard to medical applications [4].

  1. J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Kas, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophysical Journal, vol. 88, iss. 5, pp. 3689-98, 2005. doi:10.1529/biophysj.104.045476
    [BibTeX] [Download PDF]

    @Article{Guck2005,
    Title = {Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence},
    Author = {Guck, J. and Schinkinger, S. and Lincoln, B. and Wottawah, F. and Ebert, S. and Romeyke, M. and Lenz, D. and Erickson, H. M. and Ananthakrishnan, R. and Mitchell, D. and Kas, J. and Ulvick, S. and Bilby, C.},
    Journal = {{Biophysical Journal}},
    Year = {2005},
    Number = {5},
    Pages = {3689-98},
    Volume = {88},
    Doi = {10.1529/biophysj.104.045476},
    ISSN = {0006-3495 (Print)
    0006-3495 (Linking)},
    Type = {Journal Article},
    Url = {https://www.ncbi.nlm.nih.gov/pubmed/15722433
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1305515/pdf/3689.pdf}
    }

  2. Y. B. Lu, K. Franze, G. Seifert, C. Steinhauser, F. Kirchhoff, H. Wolburg, J. Guck, P. Janmey, E. Q. Wei, J. Kas, and A. Reichenbach, “Viscoelastic properties of individual glial cells and neurons in the cns,” PNAS, vol. 103, iss. 47, pp. 17759-64, 2006. doi:10.1073/pnas.0606150103
    [BibTeX] [Download PDF]

    @Article{Lu2006,
    Title = {Viscoelastic properties of individual glial cells and neurons in the CNS},
    Author = {Lu, Y. B. and Franze, K. and Seifert, G. and Steinhauser, C. and Kirchhoff, F. and Wolburg, H. and Guck, J. and Janmey, P. and Wei, E. Q. and Kas, J. and Reichenbach, A.},
    Journal = {{PNAS}},
    Year = {2006},
    Number = {47},
    Pages = {17759-64},
    Volume = {103},
    Doi = {10.1073/pnas.0606150103},
    ISSN = {0027-8424 (Print)
    0027-8424 (Linking)},
    Type = {Journal Article},
    Url = {https://www.ncbi.nlm.nih.gov/pubmed/17093050
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1693820/pdf/zpq17759.pdf}
    }

  3. A. E. Ekpenyong, G. Whyte, K. Chalut, S. Pagliara, F. Lautenschlager, C. Fiddler, S. Paschke, U. F. Keyser, E. R. Chilvers, and J. Guck, “Viscoelastic properties of differentiating blood cells are fate- and function-dependent,” PLoS One, vol. 7, iss. 9, p. e45237, 2012. doi:10.1371/journal.pone.0045237
    [BibTeX] [Download PDF]

    @Article{Ekpenyong2012,
    Title = {Viscoelastic properties of differentiating blood cells are fate- and function-dependent},
    Author = {Ekpenyong, A. E. and Whyte, G. and Chalut, K. and Pagliara, S. and Lautenschlager, F. and Fiddler, C. and Paschke, S. and Keyser, U. F. and Chilvers, E. R. and Guck, J.},
    Journal = {{PLoS One}},
    Year = {2012},
    Number = {9},
    Pages = {e45237},
    Volume = {7},
    Doi = {10.1371/journal.pone.0045237},
    ISSN = {1932-6203 (Electronic)
    1932-6203 (Linking)},
    Type = {Journal Article},
    Url = {https://www.ncbi.nlm.nih.gov/pubmed/23028868
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459925/pdf/pone.0045237.pdf}
    }

  4. J. Guck and E. R. Chilvers, “Mechanics meets medicine,” Science Translational Medicine, vol. 5, iss. 212, p. 212fs41, 2013. doi:10.1126/scitranslmed.3007731
    [BibTeX] [Download PDF]

    @Article{Guck2013,
    Title = {Mechanics meets medicine},
    Author = {Guck, J. and Chilvers, E. R.},
    Journal = {{Science Translational Medicine}},
    Year = {2013},
    Number = {212},
    Pages = {212fs41},
    Volume = {5},
    Doi = {10.1126/scitranslmed.3007731},
    ISSN = {1946-6242 (Electronic)
    1946-6234 (Linking)},
    Type = {Journal Article},
    Url = {https://www.ncbi.nlm.nih.gov/pubmed/24259047
    http://stm.sciencemag.org/content/scitransmed/5/212/212fs41.full.pdf}
    }