Surface topographies such as micrometric edges and grooves have been widely used to improve neuron outgrowth. However, finding the mechanism of neuron–surface interactions on grooved substrates remains a challenge. In this work, PC12 cells and chick forebrain neurons (CFNs) were cultured on grooved and smooth polyacrylonitrile substrates. It was found that CFNs showed a tendency of growing across groove ridges; while PC12 cells were only observed to grow in the longitudinal direction of grooves. To further investigate these observations, a 3D physical model of axonal outgrowth was developed. In this model, axon shafts are simulated as elastic 3D beams, accounting for the axon outgrowth as well as the focal contacts between axons and substrates. Moreover, the bending direction of axon tips during groove ridge crossing is governed by the energy minimization principle. Our physical model predicts that axonal groove ridge crossing is contributed by the bending compliance of axons, caused by lower Young’s modulus and smaller diameters. This work will aid the understanding of the mechanisms involved in axonal alignment and elongation of neurons guided by grooved substrates, and the obtained insights can be used to enhance the design of instructive scaffolds for nerve tissue engineering and regeneration applications.

中文翻译：

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对带槽基材上轴突生长模式的物理理解：槽脊交叉与纵向对齐

诸如测微边缘和凹槽之类的表面形貌已被广泛用于改善神经元的生长。然而，在沟槽基底上寻找神经元-表面相互作用的机制仍然是一个挑战。在这项工作中，PC12细胞和鸡前脑神经元（CFNs）培养在开槽且光滑的聚丙烯腈底物上。结果发现，CFNs呈现出越过槽脊生长的趋势。而仅观察到PC12细胞在凹槽的纵向上生长。为了进一步研究这些观察结果，开发了轴突生长的3D物理模型。在此模型中，将轴突轴模拟为弹性3D光束，考虑了轴突的扩展以及轴突与基材之间的焦点接触。此外，槽脊交叉过程中轴突尖端的弯曲方向受能量最小化原理的控制。我们的物理模型预测，轴突槽脊交叉是由较低的杨氏模量和较小的直径引起的轴突弯曲顺应性造成的。这项工作将有助于理解轴突对齐和由带槽的基质引导的神经元的伸长所涉及的机制，并且所获得的见解可用于增强对神经组织工程和再生应用的指导性支架的设计。