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Elisabeth Fischer-Friedrich - Active rheology

Since 2017 Group leader at Biotechnology Center of TU Dresden

2011-2016 Experimental biophysics postdoc jointly at the Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden and the Max-Planck-Institute for the Physics of Complex Systems, Dresden

2009-2011 Postdoctoral work at the Weizmann Institute of Sciences, Israel

2009 Doctoral degree in Physics, Saarland University

2005-2009 PhD work at the Max-Planck-Institute for the Physics of Complex Systems, Dresden

2004 Diploma in Physics, Leipzig University

Research

Many physiological processes, such as cell division or cell migration, include cellular shape changes. Like all solid-state matter, cells resist shape changes through their material stiffness. Understanding this material stiffness is therefore pivotal for our understanding of cell shape changes.  As molecular force generators produce active contractile stress in cellular material, physical concepts for inanimate matter need to be extended to capture material properties of cells. Our group works on the development of theoretical and experimental tools for the quantification of active material properties of cells.

Figure : Cell deformation in physiological processes. A) Schematic of cellular shape changes during the cell cycle. B) White blood cells squeeze through a blood vessel wall to enter inflamed tissue as part of the inflammatory response. Metastatic cancer cells undergo a similar process when they enter an organ.

 

The rheology of the cellular cortex

The cell cortex is a cytoskeletal meshwork of polymerized actin proteins that mechanically supports the inner side of the cellular plasma membrane. The cortex is constantly renewing itself through cycles of polymerization and depolymerization. Due to this turnover, it has long been hypothesized that the cortex behaves fluid-like on timescales larger than its turnover timescale. However, it was difficult to test this hypothesis experimentally as the cortex is connected to other cellular structures that generally contribute to the cellular force response in cell-mechanical probing. We have established a cell confinement assay using atomic force microscopy (AFM) that dominantly probes the cellular cortex. In this assay, we dynamically compress (non-adherent) cells between parallel plates thereby stretching the overall cell surface and thus the cortical layer of the cell. We could extract a frequency-dependent complex elastic modulus that characterizes the mechanical resistance of the cortex with respect to area dilation. Indeed, we find that the cell cortex starts to behave dominantly fluid-like for frequencies lower than ~0.01 Hz.

Figure : Our cell confinement assay. Left panel: Schematic side view. The AFM cantilever with a supplemented wedge confines a mitotic or non-adherent cell (blue). Right panel: Top view of confined cell in mitotic arrest.

 

Cortical rheology is captured by a simple rheological model

We find that cellular rheology exhibits a characteristic timescale, which marks the onset of fluidity of the cellular cortex. Still, cortical rheology is not captured by a single relaxation timescale as in the case of a simple Maxwell model. Also, a power law as commonly found in the rheology of adherent cells does not capture cortical rheology as it is devoid of a characteristic timescale. We have established a new rheological model that captures cortical rheology. This model is defined through a constant relaxation spectrum up to a cut-off timescale. This cut-off timescale corresponds to a slowest relaxation mode in the material. Our new rheological model reconciles key features of the commonly used Maxwell and power law models, because it exhibits a (slowest) characteristic timescale but also a continuum of smaller relaxation timescales. Interestingly, we find that that the slowest relaxation timescale of the cortex is similar to turnover times of cortical cross-linkers. This finding strengthens the idea that cortex fluidization stems from cortical turnover.

 

 

a)b)

Figure : a) Complex elastic modulus of the cortical sheet in mitosis measured by our cell confinement assay. b) Relaxation spectrum of our new rheological model. The relaxation spectrum relates to the relaxation modulus of the material through the relation 

Future prospects and goals

Our group establishes a new approach to cell mechanics characterizing cells as an active prestressed material. Unlike inanimate matter, cells contain molecular force generators that produce active contractile stresses in the cellular material. In cell mechanical probing, the contribution of these active stresses has been mainly disregarded. A central aim of our group is to reveal active and passive contributions to the effective cellular shear modulus conventionally used in cell mechanics. We combine experimental and theoretical work.


Publications

E. Fischer-Friedrich, Y. Toyoda, C. Cedric, D. Müller, A. Hyman, F. Jülicher, Rheology of the active cell cortex in mitosis, Biophys. J. 111:589-600, 2016


O. Otto, P. Rosendahl, A. Mietke, S. Golfier, C. Herold, D. Klaue, S. Girardo, S. Pagliara, A. Ekpenyong, A Jacobi, M. Wobus, N. Töpfner, U. F. Keyser, J. Mansfeld, E. Fischer-Friedrich, J. Guck, Real-time deformability cytometry: on-the-fly cell mechanical phenotyping, Nat. Methods 12:199-202, 2015


A. Mietke, O. Oliver, S. Girardo, P. Rosendahl, A. Taubenberger, S. Golfier, E. Ulbricht, S. Aland, J. Guck, E. Fischer-Friedrich, Extracting cell stiffness from Real-Time Deformability Cytometry - a theoretical and experimental analysis, Biophys. J. 109:2023-2036, 2015


E. Fischer-Friedrich, A. Hyman, F. Jülicher, D. Müller, J. Helenius, Quantification of surface tension and internal pressure generated by single mitotic cells, Sci. Rep. 4:6213, 2014


E. Fischer-Friedrich, N. Gov: Modeling FtsZ ring formation in the bacterial cell - anisotropic aggregation via mutual interactions of polymer rods, Phys. Biol. 8:026007, 2011.


E. Fischer-Friedrich, G. Meacci, J. Lutkenhaus, H. Chate, K. Kruse, Intra- and intercellular fluctuations in Min-protein dynamics decrease with cell length, PNAS 107:6134-9, 2010.


M. Loose, E. Fischer-Friedrich, J. Ries, K. Kruse, P. Schwille, Spatial regulators for bacterial cell division self-organize into surface waves in vitro, Science 320:789-92, 2008.

 

Group Members

You can find a list of current group members here

Open Positions

 

 

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