Effect of Dynamic Stiffness of the Substrates on Neurite Outgrowth by Using a DNA-Crosslinked Hydrogel

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Central nervous system tissues, like other tissue types, undergo constant remodeling, which potentially leads to changes in their mechanical stiffness. Moreover, mechanical compliance of central nervous system tissues can also be modified under external load such as that experienced in traumatic brain or spinal cord injury, and during pathological processes. Thus, the neuronal responses to the dynamic stiffness of the microenvironment are of significance. In this study, we induced decrease in stiffness by using a DNA-crosslinked hydrogel, and subjected rat spinal cord neurons to such dynamic stiffness. The neurons respond to the dynamic cues as evidenced by the primary neurite structure, and the response from each neurite property (e.g., axonal length and primary dendrite number) is consistent with the behavior on static gels of same substrate rigidity, with one exception of mean primary dendrite length. The results on cell population distribution confirm the neuronal responses to the dynamic stiffness. Quantification on the focal adhesion kinase expression in the neuronal cell body on dynamic gels suggests that neurons also modify adhesion in coping with the dynamic stiffnesses. The results reported here extend the neuronal mechanosensing capability to dynamic stiffness of extracellular matrix, and give rise to a novel way of engineering neurite outgrowth in time dimension.