Cell biophysics in physiology and pathology
Previous and Current Research
Cells are the basic entities of biological systems. They can be seen as little machines that have particular physical properties, which enable them to navigate their 3D physical environment and fulfil their biological functions. We investigate the physical - mechanical and optical - properties of living cells and tissues using novel photonics and biophysical tools to test their biological importance. Our ultimate goal is the transfer of our findings to medical application in the fields of improved diagnosis of diseases and novel approaches in regenerative medicine.
Our recent findings increasingly demonstrate that the mechanical properties of cells determine the physical limits of cell function – for example in 3D cell migration. Cell mechanics can thus be used to characterise cells, to monitor physiological changes (such as stem cell differentiation), and to diagnose pathological alterations (such as metastatic progression or inflammatory reactions). We are developing novel label-free, high-throughput cell analysis methods to transfer these basic findings into clinical practice. Publications: J. Guck & E.R. Chilvers. Mechanics meets medicine. Science Translational Medicine, 5(212), 212fs41 (2013); O. Otto, et al. Real-time deformability cytometry: on-the-fly cell mechanical phenotyping. Nature Methods, 12(3), 199–202 (2015).
Mechanosensing and Tissue Mechanics in the CNS
It is increasingly recognised that cells react to the mechanical properties of their environment and that these mechanical cues can be as important as adhesive or soluble biochemical cues. We are especially interested in assessing the importance of this “mechanosensing” in the development and in pathological conditions in the central nervous system. For reviews, see: K. Franze and J.Guck, The biophysics of neuronal regrowth Rep. Progr. Phys. 73:094601 (2010); K. Franze, P.A. Janmey, & J. Guck. Mechanics in Neuronal Development and Repair. Annu Rev Biomed Eng, 15(1), 227–251 (2013). Oligodendrocytes, microglia, astrocytes, and neurons have all been shown to react to the stiffness of their environment (A. Jagielska, et al. Mechanical Environment Modulates Biological Properties of Oligodendrocyte Progenitor Cells. Stem Cells Dev. 21(16), 2905–2914, 2012; Moshayedi et al. The relationship between glial cell mechanosensitivity and foreign body reactions in the central nervous system. Biomaterials, 35(13), 3919–3925, 2014). We are now starting to test these ideas in vivo.
Cell and Tissue Optics
Another example for the importance of physics in biology are the optical properties of cells, specifically in the retina, which is, curiously, inverted with respect to its optical function. The light-sensing photoreceptor cells are located on the 'wrong' side - the side furthest away from the incoming light. Consequently, light has to traverse hundreds of microns of potentially scattering tissue. We have shown that there are cells in the retina that act as optical fibers (K. Franze et al., Müller cells are living optical fibers in the vertebrate retina. Proc. Natl. Acad. Sci. U.S.A. 104:8287-9292; 2007) and that photoreceptor cells even invert their usual nuclear chromatin arrangement to turn them into microlenses (I. Solovei et al., Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution. Cell 137:356-368, 2009). There are also very specialized retinal arrangements in certain types of fish (M. Kreysing, et al. Photonic crystal light collectors in fish retina improve vision in turbid water. Science, 336(6089), 1700–1703, 2012). All these physical specializations improve the light transmission through the retina and shed new light on the retina as an optical system. Our latest research also has uncovered surprising optical properties of other cell nuclei (M. Schürmann, et al. Cell nuclei have lower refractive index and mass density than cytoplasm. J. Biophot. doi.org/10.1002/jbio.201500273, 2016).
Future Projects and Goals
We continue to investigate cell mechanics as diagnostic marker – increasingly for the diagnosis of sepsis and other inflammatory conditions – and to characterize the mechanical properties of individual cells in the context of differentiation and development. Both technological and biological/biomedical projects are available.
We will increasingly work on the mechanical properties of CNS tissue (retina, brain, spinal cord) and their importance during development and implications for lack of axonal regrowth or remyelination after injury or of demyelinating conditions (such as multiple sclerosis). Possible projects include measurement of tissue mechanics with AFM or mimicking 3D tissue mechanics in vitro. We are also involved in studies into the improved biocompatibility of neural implants and prosthetic devices.
Methodological and Technical Expertise
- Optical trapping and micromanipulation
- Scanning force microscopy
- Cell and tissue mechanical measurements
- Quantitative phase microscopy
M. C. Munder, D. Midtvedt, T. Franzmann, E. Nüske, O. Otto, M. Herbig, E. Ulbricht, P. Müller, A. Taubenberger, S. Maharana, L. Malinovska, D. Richter, J. Guck, V. Zaburdaev and S. Alberti.
A pH-driven transition of the cytoplasm from a fluid- to a solid-like state promotes entry into dormancy.
eLife 5:e09347 (2016).
O. Otto, Ph. Rosendahl, A. Mietke, S. Golfier, Ch. Herold, D. Klaue, S. Girardo, S. Pagliara, A. Ekpenyong, A. Jacobi, M. Wobus, N. Töpfner, U. F. Keyser, J. Mansfeld, E. Fischer-Friedrich, and J. Guck
Real-time deformability cytometry: on-the-fly cell mechanical phenotyping
Nat. Methods 12(3):199–202 (2015).
P. Moshayedi, G. Ng, J. C. F. Kwok, G. S. H. Yeo, C. E. Bryant, J. W. Fawcett, K. Franze, and J. Guck.
The relationship between glial cell mechanosensitivity and foreign body reactions in the central nervous system.
Biomaterials 35(13):3919–3925 (2014).
M. Kreysing, et al.
Photonic crystal light collectors in fish retina improve vision in turbid water.
Science 336(6089):1700–1703. (2012)
I. Solovei, M. Kreysing, Ch. Lanctôt, S. Kösem, L. Peichl, Th. Cremer, J. Guck*, and B. Joffe*
Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution.
Cell 137(2):356–68 (2009) [* joint corresponding authors]