ZiMT Journal Club November 2020: Prof. Kristian Franze / How mechanics regulate biological processes in the nervous system

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Prof. Kristian Franze, Chair of Medical Physics and Microtissue Engineering, FAU and Max-Planck-Zentrum für Physik und Medizin

How mechanics regulate biological processes in the nervous system

The development of the central nervous system (CNS) includes the formation of neuronal axons, their subsequent growth and guidance through thick layers of nervous tissue, and the folding of the brain. All these processes involve motion and must thus be driven by forces. However, the contribution of mechanics remains poorly understood. Cell motion is also crucially involved in the regeneration of neurons after CNS (e.g., spinal cord) injuries. So far, research has – without any major breakthrough – mainly focused on chemical signals impeding and promoting neuronal (re)growth.

We are taking a different, interdisciplinary approach and investigate how cellular forces, local cell and tissue compliance and cellular mechanosensitivity contribute to CNS development, disease and regeneration. Methods include atomic force microscopy, traction force microscopy, custom-built simple and complex compliant cell culture substrates, optical microscopy including confocal laser scanning microscopy and cell biology techniques. We have shown that nervous tissue is mechanically highly heterogeneous. Neurons constantly exert forces on their environment, and both neurons and glial cells respond to mechanical cues such as tissue stiffness. Understanding how and when CNS cells actively exert forces and respond to their mechanical environment will shed new light on CNS development, and it could eventually lead to novel biomedical approaches to treat or circumvent pathologies and injuries that involve mechanical signalling.

References

Rheinlaender J, Dimitracopoulos A, Wallmeyer B, Kronenberg NM, Chalut KJ, Gather MC, Betz T, Charras G, Franze K: Cortical cell stiffness is independent of substrate mechanics Nature Materials 19:1019–1025 (2020)

Jakobs MAH, Dimitracopoulos A, Franze K: KymoButler, a deep learning software for automated kymograph analysis eLife 8:e42288 (2019)

Thompson AJ, Pillai EK, Dimov IB, Foster SK, Holt CE, Franze K: Rapid changes in tissue mechanics regulate cell behaviour in the developing embryonic brain eLife 8:e39356 (2019)

Barriga EH, Franze K, Charras G, Mayor R: Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo Nature doi:10.1038/nature25742 (2018)

Moeendarbary E, Weber IP, Sheridan GK, Koser DE, Solemane S, Haenzie B, Bradbury EJ, Fawcett J, Franze K: The soft mechanical signature of glial scars in the central nervous system Nature Communications 8:14787 (2017)

Koser DE, Thompson AJ, Foster SK, Dwivedy A, Pillai EK, Sheridan GK, Svoboda H, Viana M, Costa LdF, Guck J, Holt CE, Franze K: Mechanosensing is critical for axon growth in the developing brain Nature Neuroscience 19(12):1592-1598 (2016)