Yurchenko Ilya, Farwell Matthew, Brady Donovan D, Staii Cristian
Department of Physics and Astronomy, Tufts University, Medford, MA 02155, USA.
Biomimetics (Basel). 2021 Jun 16;6(2):41. doi: 10.3390/biomimetics6020041.
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.
神经元网络的形成是一个至关重要的过程，对于理解神经系统的发育以及创建用于组织工程和神经修复的仿生装置都具有重要意义。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。轴突生长受环境刺激的引导，这些刺激包括细胞间相互作用、生化信号以及生长底物的机械和几何特性。尽管最近取得了重大进展，但对生长中轴突的导向仍知之甚少。在本文中，我们开发了一个包含底物几何形状感知的轴突运动模型。我们将实验数据与理论分析相结合，以测量描述轴突在微图案表面生长的参数：扩散（细胞运动）系数、速度和角度分布以及细胞 - 底物相互作用。在用微管抑制剂（紫杉醇）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，细胞骨架动力学在导向机制中起关键作用。我们的结果表明，轴突通过接触导向机制遵循几何图案，其中几何图案对生长锥施加高牵引力。这些结果对生物工程新型底物以引导神经元生长和促进神经修复具有重要意义。
