方向面上的神经元生长和神经元网络的形成
Neuronal Growth and Formation of Neuron Networks on Directional Surfaces
摘要：
神经元网络的形成对于理解神经系统的发育以及对于创建用于组织工程和神经修复的仿生装置是具有根本重要性的过程。控制网络形成的基本过程是轴突从细胞体生长并向靶神经元延伸。轴突的生长是由环境刺激，包括细胞间的相互作用，生物化学线索，和生长基质的机械和几何特性。尽管最近取得了重大进展，但对轴突生长的控制仍然知之甚少。在本文中，我们开发了一个模型的轴突运动，其中包括基板几何传感。我们将实验数据与理论分析相结合，以测量描述轴突生长的微图案化表面的参数：扩散（细胞运动）系数，速度和角分布，和细胞-基质相互作用。在用微管抑制剂（泰素）和肌动蛋白丝抑制剂（Y-27632）处理的神经元上进行的实验表明，细胞骨架动力学在转向机制中起关键作用。我们的研究结果表明，轴突通过接触引导机制，其中几何图案赋予高牵引力的生长锥的几何图案。这些结果对指导神经生长和促进神经修复的生物工程新底物具有重要意义。
英文摘要：
The formation of neuron networks is a process of fundamental importance for understanding the development of the nervous system and for creating biomimetic devices for tissue engineering and neural repair. The basic process that controls the network formation is the growth of an axon from the cell body and its extension towards target neurons. Axonal growth is directed by environmental stimuli that include intercellular interactions, biochemical cues, and the mechanical and geometrical properties of the growth substrate. Despite significant recent progress, the steering of the growing axon remains poorly understood. In this paper, we develop a model of axonal motility, which incorporates substrate-geometry sensing. We combine experimental data with theoretical analysis to measure the parameters that describe axonal growth on micropatterned surfaces: diffusion (cell motility) coefficients, speed and angular distributions, and cell-substrate interactions. Experiments performed on neurons treated with inhibitors for microtubules (Taxol) and actin filaments (Y-27632) indicate that cytoskeletal dynamics play a critical role in the steering mechanism. Our results demonstrate that axons follow geometrical patterns through a contact-guidance mechanism, in which geometrical patterns impart high traction forces to the growth cone. These results have important implications for bioengineering novel substrates to guide neuronal growth and promote nerve repair.
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