Substrate stiffness affects neural network activity in an extracellular matrix proteins dependent manner.
Substrate stiffness affects neural network activity in an extracellular matrix proteins dependent manner.
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DOI：
10.1016/j.colsurfb.2018.03.042
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发表时间：
2018-10
期刊：
影响因子：
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通讯作者：
Yuqiao Wen;Xiaohui Gao;Aiping Wang;Yu Yang;Sisi Liu;Zhang Yu;Guan-Bing Song;Hucheng Zhao
中科院分区：
文献类型：
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作者：
Yuqiao Wen;Xiaohui Gao;Aiping Wang;Yu Yang;Sisi Liu;Zhang Yu;Guan-Bing Song;Hucheng Zhao
细胞外基质（extracellular matrix， ECM）的力学性质对神经元的生长、分化、伸展、分支和神经网络活动有重要影响。然而，衬底刚度调节神经网络活动的机制，以及ECM组成在赋予衬底刚度感知中的重要性尚未得到探讨。为了解决这个问题，我们将海马神经元植入不同硬度的聚二甲基硅氧烷（PDMS）底物上，分别涂覆纤维连接蛋白和层粘连蛋白。我们的研究结果表明，电压门控Ca2+通道电流在硬基质上比在软基质上的神经元更大。此外，在膜粘连蛋白包被的硬底物上，神经元的Ca2+电流比包被纤维连接蛋白的神经元的Ca2+电流增加更大，表明ECM的组成可以调节神经元对底物刚度的反应。成对膜片钳记录显示，在层粘连蛋白涂覆的硬基质上，神经有效突触连通性的上调比在纤维连接蛋白涂覆的硬基质上更大。一致地，层粘连蛋白涂层的硬底物增强神经元的Ca2+振荡比纤维连接蛋白涂层的神经元更大。我们的研究表明，基底刚度在调节神经元网络活动中的直接作用，并表明这种调节依赖于特定类型的ECM蛋白，这应该考虑到神经组织工程生物材料的设计。
Neuronal growth, differentiation, extension, branching and neural network activity are strongly influenced by the mechanical property of extracellular matrix (ECM). However, the mechanism by which substrate stiffness regulates a neural network activity, and the importance of ECM composition in conferring substrate stiffness sensing have not been explored. To address this question, the hippocampal neurons were seeded on the polydimethylsiloxane (PDMS) substrate with different stiffness, which were coated with fibronectin and laminin respectively. Our results show that voltage-gated Ca2+channel currents are greater in neurons on the stiff substrate than on the soft substrate. In addition, the neurons exhibit a greater increase of Ca2+currents on laminin-coated stiff substrate than on those coated with fibronectin, indicating that the composition of ECM can modulate responses to substrate stiffness of neurons. Paired patch-clamp recordings have shown that upregulation of neural effective synaptic connectivity is greater on the laminin-coated stiff substrate than on the fibronectin-coated ones. Consistently, laminin-coated stiff substrate enhances Ca2+oscillations of neurons is greater that compared with the fibronectin-coated ones. Our study demonstrates that a direct role for substrate stiffness in regulating neuronal network activity and indicate that this modulation is dependent on a specific type of ECM protein, which should be taken into account for the design of biomaterials for neuronal tissue engineering.