While nanoscale modification of a biomaterial surface is known to influence various cell behaviors, it is unclear whether there is an optimal nanospacing of a bioactive ligand with respect to cell migration. Herein, we investigated the effects of nanospacing of arginine-glycine-aspartate (RGD) peptide on cell migration and its relation to cell adhesion. To this end, we prepared RGD nanopatterns with varied nanospacings (31–125 nm) against the nonfouling background of poly(ethylene glycol), and employed human umbilical vein endothelial cells (HUVECs) to examine cell behaviors on the nanopatterned surfaces. While HUVECs adhered well on surfaces of RGD nanospacing less than 70 nm and exhibited a monotonic decrease of adhesion with the increase of RGD nanospacing, cell migration exhibited a nonmonotonic change with the ligand nanospacing: the maximum migration velocity was observed around 90 nm of nanospacing, and slow or very slow migration occurred in the cases of small or large RGD nanospacings. Therefore, moderate cell adhesion is beneficial for fast cell migration. Further molecular biology studies revealed that attenuated cell adhesion and activated dynamic actin rearrangement accounted for the promotion of cell migration, and the genes of small G proteins such as Cdc42 were upregulated correspondingly. The present study sheds new light on cell migration and its relation to cell adhesion, and paves a way for designing biomaterials for applications in regenerative medicine.

虽然已知生物材料表面的纳米级修饰会影响各种细胞行为，但尚不清楚生物活性配体相对于细胞迁移是否具有最佳的纳米间距。在这里，我们研究了精氨酸-甘氨酸-天冬氨酸（RGD）肽的纳米间距对细胞迁移的影响及其与细胞粘附的关系。为此，我们准备了在聚乙二醇无污染背景下具有不同纳米间距（31–125 nm）的RGD纳米图案，并使用人脐静脉内皮细胞（HUVEC）来检查纳米图案表面上的细胞行为。当HUVECs在小于70 nm的RGD纳米间距的表面上很好地粘附并且随着RGD纳米间距的增加表现出粘附力的单调下降时，随着配体的纳米间距，细胞迁移表现出非单调变化：在纳米间距为90 nm处观察到最大迁移速度，而在RGD纳米间距较小或较大的情况下，迁移速度会非常缓慢。因此，适度的细胞粘附有利于细胞的快速迁移。进一步的分子生物学研究表明，减弱的细胞粘附和激活的动态肌动蛋白重排是促进细胞迁移的原因，小G蛋白（如Cdc42）的基因也相应上调。本研究为细胞迁移及其与细胞粘附的关系提供了新的思路，并为设计用于再生医学的生物材料铺平了道路。适度的细胞粘附有利于细胞快速迁移。进一步的分子生物学研究表明，减弱的细胞粘附和激活的动态肌动蛋白重排是促进细胞迁移的原因，小G蛋白（如Cdc42）的基因也相应上调。本研究为细胞迁移及其与细胞粘附的关系提供了新的思路，并为设计用于再生医学的生物材料铺平了道路。适度的细胞粘附有利于细胞快速迁移。进一步的分子生物学研究表明，减弱的细胞粘附和激活的动态肌动蛋白重排是促进细胞迁移的原因，小G蛋白（如Cdc42）的基因也相应上调。本研究为细胞迁移及其与细胞粘附的关系提供了新的思路，并为设计用于再生医学的生物材料铺平了道路。