Hydrogels with tunable mechanical properties have provided a tremendous opportunity to regulate stem cell differentiation. Hydrogels with osteoid (about 30–40 kPa) or higher stiffness are usually required to induce the osteogenic differentiation of mesenchymal stem cells (MSCs). It is yet difficult to achieve the same differentiation on very soft hydrogels, because of low environmental mechanical stimuli and restricted cellular mechanotransduction. Here, we modulate cellular spatial sensing of integrin-adhesive ligands via quasi-hexagonally arranged nanopatterns to promote cell mechanosensing on hydrogels having low stiffness (about 3 kPa). The increased interligand spacing has been shown to regulate actomyosin force loading to recruit extra integrins on soft hydrogels. It therefore activates mechanotransduction and promotes the osteogenic differentiation of MSCs on soft hydrogels to the level comparable with the one observed on osteoid stiffness. Our work opens up new possibilities for the design of biomaterials and tissue scaffolds for regenerative therapeutics.

具有可调机械性能的水凝胶为调节干细胞分化提供了巨大的机会。通常需要具有类骨质（约30–40 kPa）或更高硬度的水凝胶来诱导间充质干细胞（MSC）的成骨分化。由于非常低的环境机械刺激和受限制的细胞机械转导，在非常柔软的水凝胶上很难实现同样的分化。在这里，我们通过准六边形排列的纳米模式来调节整联蛋白-粘附配体的细胞空间感测，以促进具有低刚度（约3 kPa）的水凝胶的细胞机械传感。已显示增加的配体间距可调节肌动球蛋白力负荷以在软水凝胶上募集额外的整合素。因此，它激活了机械转导，并促进了软水凝胶上的MSC的成骨分化，其水平与类骨质刚度所观察到的水平相当。我们的工作为再生疗法的生物材料和组织支架的设计开辟了新的可能性。