The microenvironment of developing neurons is a dynamic landscape of both chemical and mechanical cues that regulate cell proliferation, differentiation, migration, and axon extension. While the regulatory roles of chemical ligands in neuronal morphogenesis have been described, little is known about how mechanical forces influence neurite development. Here, we tested how substratum elasticity regulates neurite development of human forebrain (hFB) neurons and human motor neurons (hMNs), two populations of neurons that naturally extend axons into distinct elastic environments. Using polyacrylamide and collagen hydrogels of varying compliance, we find that hMNs preferred rigid conditions that approximate the elasticity of muscle, whereas hFB neurons preferred softer conditions that approximate brain tissue elasticity. More stable leading-edge protrusions, increased peripheral adhesions, and elevated RHOA signaling of hMN growth cones contributed to faster neurite outgrowth on rigid substrata. Our data suggest that RHOA balances contractile and adhesive forces in response to substratum elasticity.

发育中的神经元的微环境是调节细胞增殖、分化、迁移和轴突延伸的化学和机械线索的动态景观。虽然已经描述了化学配体在神经元形态发生中的调节作用，但对于机械力如何影响轴突发育知之甚少。在这里，我们测试了底层弹性如何调节人类前脑 (hFB) 神经元和人类运动神经元 (hMN) 的神经突发育，这两个神经元群自然地将轴突延伸到不同的弹性环境中。使用不同顺应性的聚丙烯酰胺和胶原水凝胶，我们发现 hMN 更喜欢接近肌肉弹性的刚性条件，而 hFB 神经元更喜欢接近脑组织弹性的较软条件。更稳定的前缘突起、增加的外周粘连和升高的 hMN 生长锥的 RHOA 信号有助于在刚性基质上更快地生长神经突。我们的数据表明 RHOA 平衡收缩力和粘附力以响应基质弹性。