It is increasingly recognized that cells measure and respond to the mechanics of their environment. We are especially interested in this mechanosensing during CNS development and pathologies. Using quantitative scanning force microscopy we have shown that various neural tissues are very compliant (shear modulus < 1 kPa) and mechanically heterogeneous. We have recreated compliant polyacrylamide gel substrate with shear moduli between 0.1 and 30 kPa to match and exceed those of CNS tissue. Various primary neurons and glial cells have been cultured on these gels and their reaction studied. Both primary microglia and astrocytes responded to increasing substrate stiffness by changes in morphology and upregulation of inflammatory genes. Upon implantation of composite hydrogel stripes into rat brains, foreign body reactions were significantly enhanced around the stiff parts of the implant. It appears that the mechanical mismatch between a neural implant and native tissue might be at the root of foreign body reactions. Also oligodendrocytes are mechanosensitive as their survival, proliferation, migration, and differentiation capacity in vitro depend on substrate stiffness. This finding might be linked to the failure of remyelination in chronic demyelinating diseases such as multiple sclerosis. And finally, we have also shown retinal ganglion axon pathfinding in the early embryonic Xenopus brain development to be instructed by stiffness gradients. These results form the basis for further investigations into the mechanobiology of cell function in the CNS. Ultimately, this research could help treating previously incurable neuropathologies such as spinal cord injuries and neurodegenerative disorders.

Date Published: 24 April 2017
PDF: 1 pages
Proc. SPIE 10067, Optical Elastography and Tissue Biomechanics IV, 100670A (24 April 2017); doi: 10.1117/12.2256083

Published in SPIE Proceedings Vol. 10067:
Optical Elastography and Tissue Biomechanics IV
Kirill V. Larin; David D. Sampson, Editor(s)