Measuring and manipulating in vivo tissue mechanics using AFM

Session

AFM in Life Sciences

Authors

Kristian Franze (1, 2, 3)

Affiliations

1. University of Cambridge
2. FAU Erlangen-Nürnberg
3. Max-Planck-Zentrum für Physik und Medizin

Keywords

in vivo AFM, axon growth, tissue mechanics, mechanotransduction, Piezo1

Abstract text

During brain morphogenesis, neurons are highly motile. However, even though motion is driven by forces, our current understanding of the physical interactions between neurons and their environment is very limited. We here show how local mechanical brain tissue properties contribute to specifying and guiding neuronal axons.  In vivo time-lapse atomic force microscopy revealed viscoelasticity gradients in developing brain tissue, which axons followed towards soft. Interfering with brain stiffness and mechanosensitive ion channels in vivo both led to aberrant neuronal growth patterns with reduced fasciculation and pathfinding errors. Moreover, mechanical signals not only directly impacted neuronal growth but also indirectly by regulating neuronal responses to and the availability of chemical guidance cues, strongly suggesting that chemical and mechanical signaling pathways are intimately linked, and that their interaction is crucial for morphogenetic events.

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) 

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) 

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)