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

Man Zhang, Qian Sun, Yiling Liu, Zhiqin Chu, Leixiao Yu, Yong Hou, Heemin Kang, Qiang Wei, Weifeng Zhao, Joachim P. Spatz, Changsheng Zhao, Elisabetta A. Cavalcanti-Adam

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


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.

Original languageEnglish
Article number120543
Publication statusPublished - 2021 Jan

Bibliographical note

Funding Information:
We acknowledge the financial support from National Key R&D Program of China (Grant Nos. 2018YFC1106800 , 2016YFC1103000 and 2018YFC1106400 ) and National Natural Science Foundation of China (Grant Nos. 51973129 , 51773127 and 51873115 ), China Scholarship Council (the State Scholarship Fund) and Max Planck Society . E.A. Cavalcanti-Adam alo acknowledges the support from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 872869 .

Publisher Copyright:
© 2020 Elsevier Ltd


  • Differentiation
  • Hydrogel
  • Ligand spacing
  • Mechanotransduction
  • Mesenchymal stem cell

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials


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