Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
Tissue Eng Part A. 2010 Jun;16(6):1873-89. doi: 10.1089/ten.TEA.2009.0574.
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.
中枢神经系统组织与其他组织类型一样，会不断进行重塑，这可能导致其机械硬度发生变化。此外，中枢神经系统组织的机械顺应性也可以在外力作用下发生改变，如在创伤性脑或脊髓损伤以及在病理过程中。因此，神经元对微环境动态刚度的反应具有重要意义。在这项研究中，我们使用 DNA 交联水凝胶来降低硬度，并使大鼠脊髓神经元适应这种动态硬度。神经元对动态线索做出反应，这可以从初级轴突结构中得到证明，并且每个轴突属性（例如，轴突长度和初级树突数量）的反应与具有相同基质刚性的静态凝胶上的行为一致，只有一个例外，即平均初级树突长度。细胞群体分布的结果证实了神经元对动态刚度的反应。对动态凝胶上神经元细胞体中粘着斑激酶表达的定量分析表明，神经元也通过改变黏附来应对动态刚度。这里报告的结果将神经元的机械传感能力扩展到细胞外基质的动态刚度，并为在时间维度上构建神经突生长提供了一种新方法。
