Invited Talk

Mechanics matters for cells: From extracellular matrix via cytoskeleton to the nucleus

Georg-August-University Göttingen, Third Institute of Physics – Biophysics, Friedrich-Hund-Platz 1, 37077 Göttingen, Germany

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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).