Controllable ligand spacing stimulates cellular mechanotransduction and promotes stem cell osteogenic differentiation on soft hydrogels

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 ar ranged 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.

Automated summary

Tunable mechanical properties of hydrogels play a key role in regulating stem cell differentiation. By modulating cellular spatial sensing of integrin-adhesive ligands on low stiffness hydrogels, the mechanosensing and osteogenic differentiation of MSCs can be promoted to levels comparable with those observed on stiffer hydrogels. This approach opens up new possibilities for designing biomaterials and tissue scaffolds for regenerative therapeutics.