Tissue Mechanics

Cells define and largely form their surrounding tissues and, in return, receive biochemical and physical cues from them. We are working on resolving this interdependence by quantifying these tissue mechanical properties, correlating them with biological function, investigating their origin and ultimately controlling them.
It is fairly well established by now that most, if not all, cells respond to mechanical cues of their microenvironment (see Mechanosensing) [1]. We are interested in understanding how the mechanical properties of tissues in vivo influence cellular behaviour in essential processes such as development and in general under homeostatic and pathological conditions. Thus, we investigate the mechanical properties of different soft tissues, such as neural and adipose tissues, at cellular resolution. For this we conduct indentation measurements by atomic force microscopy (AFM) optimized for such soft tissue samples [2, 3]. We combine these tissue mechanical measurements with a correlation of biological function during development, aging and pathology. For example, we have been working on the notion that neuronal growth is guided by mechanical cues. Mapping the mechanical properties of brain tissue using AFM in vivo revealed that the growth of the optic tract in Xenopus laevis is indeed following mechanical patterns [4]. Adverse mechanical properties of brain tissue after demyelination, for example in multiple sclerosis, might also lead to insufficient remyelination because of the mechanosensitivity of oligodendrocyte precursor cells [5].
To fully demonstrate that the mechanical properties are causative for normal or aberrant cell biological function we need to be able to intentionally tune these properties. While the key components of tissue architecture — cell types, extracellular matrix, intercellular connectivity and specific structures such as the capillary network — are in general well known, we still do not know whether and how these individual components contribute to defining the mechanical properties of the entire tissue. Hence, we have started to correlate quantitative tissue mechanical maps with advanced morphological analysis and their constituent make-up. Controlling tissue mechanical properties might eventually lead to entirely new therapeutic options for treating currently incurable neurological disorders.

An important technological approach towards this goal is also the realistic mimicking of 3D tissue mechanics in vitro . This allows us to examine and influence cellular behavior in response to altering the mechanical properties while fully controlling other parameters such as biochemistry or the topology of the cellular surrounding.

 


[1]   P. Moshayedi, L. F. da Costa, A. F. Christ, S. P. Lacour, J. Fawcett, J. Guck, and K. Franze, “Mechanosensitivity of astrocytes on optimized polyacrylamide gels analyzed by quantitative morphometry,” Journal of Physics: Condensed Matter, vol. 22, iss. 19, p. 194114, 2010. 

[2]   A. F. Christ, K. Franze, H. Gautier, P. Moshayedi, J. Fawcett, R. J. M. Franklin, R. T. Karadottir, and J. Guck, “Mechanical difference between white and gray matter in the rat cerebellum measured by scanning force microscopy,” Journal of Biomechanics, vol. 43, iss. 15, pp. 2986-2992, 2010. 

[3]   K. Franze, M. Francke, K. Günter, A. F. Christ, N. Körber, A. Reichenbach, and J. Guck, “Spatial mapping of the mechanical properties of the living retina using scanning force microscopy,” Soft matter, vol. 7, iss. 7, p. 3147–3154, 2011. 

[4]   D. E. Koser, A. J. Thompson, S. K. Foster, A. Dwivedy, E. K. Pillai, G. K. Sheridan, H. Svoboda, M. Viana, L. F. da Costa, J. Guck, C. E. Holt, and K. Franze, “Mechanosensing is critical for axon growth in the developing brain,” Nature Neuroscience, vol. 19, iss. 12, p. 1592–1598, 2016. 

[5]   A. Jagielska, A. L. Norman, G. Whyte, K. V. J. Vliet, J. Guck, and R. J. M. Franklin, “Mechanical Environment Modulates Biological Properties of Oligodendrocyte Progenitor Cells,” Stem Cells and Development, vol. 21, iss. 16, 2012. 

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