9th Annual Symposium
Physics of Cancer
Leipzig, Germany
September 24-26, 2018
Invited Talk
Mechanics matters for cells: From extracellular matrix via cytoskeleton to the nucleus
Florian Rehfeldt
Georg-August-University Göttingen, Third Institute of Physics – Biophysics, Friedrich-Hund-Platz 1, 37077 Göttingen, Germany
Contact:  | Website
The mechanical properties of microenvironments in our body vary over a broad range and are as important for cells as biochemical cues. An especially striking experiment of this mechano-sensitivity demonstrated that systematic variation of the Young’s elastic modulus E of the substrate can direct the lineage differentiation of human mesenchymal stem cells (hMSCs) (1).

To elucidate the complex interplay of physical and biochemical mechanisms of cellular mechano-sensing, well-defined extracellular matrix (ECM) models are essential. While elastic substrates made of poly-acrylamide (PA) are widely in use, they have the potential drawback that the precursors are cytotoxic and therefore do not allow for 3D culture systems. Here, a novel biomimetic ECM model based on hyaluronic acid (HA) was successfully established that exhibits a widely tuneable and well-defined elasticity E, allows for 2D and 3D cell culture and enables us to mimic a variety of distinct in vivo microenvironments (2). Quantitative analysis of the structure of acto-myosin fibers of hMSCs on elastic substrates by an order parameter S, reveals that the stress fiber morphology is an early morphological marker of mechano-guided differentiation and can be understood using a classical mechanics model (3). Furthermore, the cytoskeleton also dictates the shape of the nucleus and lends support to a direct mechanical matrix-myosin-nucleus pathway (4).
I will also highlight some of our recent approaches to quantify the cytoskeleton structure during massively parallel life cell imaging with our new tool filament sensor (5), by scanning x-ray microscopy (6), and about elucidating the 3D architecture of focal adhesions using metal induced energy transfer (MIET) combined with FRET (7).
[1]Engler, A. J., S. Sen, H. L. Sweeney, and D. E. DischerMatrix Elasticity Directs Stem Cell Lineage Specification, Cell 126:677-689 (2006)
[2]Rehfeldt, F., A. E. X. Brown, M. Raab, S. Cai, A. L. Zajac, A. Zemel, and D. E. DischerHyaluronic acid matrices show matrix stiffness in 2D and 3D dictates cytoskeletal order and myosin-II phosphorylation within stem cells, Integrative Biology 4:422-430 (2012)
[3]Zemel, A., F. Rehfeldt, A. E. X. Brown, D. E. Discher, and S. A. SafranOptimal matrix rigidity for stress-fibre polarization in stem cells, Nature Physics 6:468-473 (2010)
[4]Swift, J., I. L. Ivanovska, A. Buxboim, T. Harada, P. C. D. P. Dingal, J. Pinter, J. D. Pajerowski, K. R. Spinler, J.-W. Shin, and M. TewariNuclear Lamin-A Scales with Tissue Stiffness and Enhances Matrix-Directed Differentiation, Science 341 (2013)
[5]Eltzner, B., C. Wollnik, C. Gottschlich, S. Huckemann, and F. RehfeldtThe Filament Sensor for Near Real-Time Detection of Cytoskeletal Fiber Structures, PLOS ONE 10:e0126346 (2015)
[6]Bernhardt, M., M. Priebe, M. Osterhoff, C. Wollnik, A. Diaz, T. Salditt, and F. RehfeldtX-Ray Micro- and Nanodiffraction Imaging on Human Mesenchymal Stem Cells and Differentiated Cells, Biophysical Journal 110:680-690 (2016)
[7]Chizhik, A. M., C. Wollnik, D. Ruhlandt, N. Karedla, A. I. Chizhik, L. Hauke, D. Hähnel, I. Gregor, J. Enderlein, and F. RehfeldtDual-color metal-induced and förster resonance energy transfer for cell nanoscopy, Molecular Biology of the Cell (2018)
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