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

doi:10.1016/j.biomaterials.2020.120543

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

Biomaterials. 2021 Jan:268:120543. doi: 10.1016/j.biomaterials.2020.120543. Epub 2020 Nov 23.

Authors

Man Zhang¹, Qian Sun², Yiling Liu², Zhiqin Chu³, Leixiao Yu⁴, Yong Hou⁴, Heemin Kang⁵, Qiang Wei⁶, Weifeng Zhao⁷, Joachim P Spatz⁸, Changsheng Zhao⁹, Elisabetta A Cavalcanti-Adam⁸

Affiliations

¹ College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials and Engineering, Sichuan University, 610065, Chengdu, China; Department of Cellular Biophysics, Max Planck Institute for Medical Research, Jahnstraße 29, 69120, Heidelberg, Germany; Department of Biophysical Chemistry, Heidelberg University, INF 253, 69120, Heidelberg, Germany.
² College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials and Engineering, Sichuan University, 610065, Chengdu, China.
³ Department of Electrical and Electronic Engineering, Joint Appointment with School of Biomedical Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
⁴ Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
⁵ Department of Biomicrosystem Technology, Korea University, Seoul, 02841, Republic of Korea.
⁶ College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials and Engineering, Sichuan University, 610065, Chengdu, China; College of Biomedical Engineering, Sichuan University, 610064, Chengdu, China. Electronic address: wei@scu.edu.cn.
⁷ College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials and Engineering, Sichuan University, 610065, Chengdu, China. Electronic address: zhaoscukth@163.com.
⁸ Department of Cellular Biophysics, Max Planck Institute for Medical Research, Jahnstraße 29, 69120, Heidelberg, Germany; Department of Biophysical Chemistry, Heidelberg University, INF 253, 69120, Heidelberg, Germany.
⁹ College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials and Engineering, Sichuan University, 610065, Chengdu, China; College of Biomedical Engineering, Sichuan University, 610064, Chengdu, China.

PMID: 33260094
DOI: 10.1016/j.biomaterials.2020.120543

Abstract

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.

Keywords: Differentiation; Hydrogel; Ligand spacing; Mechanotransduction; Mesenchymal stem cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation
Hydrogels
Ligands
Mechanotransduction, Cellular*
Osteogenesis*

Substances

Hydrogels
Ligands