Receptor-Level Proximity and Fastening of Ligands Modulates Stem Cell Differentiation

Gunhyu Bae, Myeong Soo Kim, Ramar Thangam, Thomas Myeongseok Koo, Woo Young Jang, Jinho Yoon, Seong Beom Han, Letao Yang, Seong Yeol Kim, Nayeon Kang, Sunhong Min, Hyunsik Hong, Hong En Fu, Min Jun Ko, Dong Hwee Kim, Woong-Kyo Jeong, Dong Hyun Kim, Tae Hyung Kim, Jeong Woo Choi, Ki Bum LeeRamasamy Paulmurugan, Yangzhi Zhu, Han Jun Kim, Junmin Lee, Jong Seung Kim, Ali Khademhosseini, Young Keun Kim, Heemin Kang

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Cellular adhesion is regulated by the binding of 10 nm sized integrin to Arg-Gly-Asp (RGD) ligands present in extracellular matrix proteins. In this study, seed-mediated growth of gold nanoparticles (AuNPs) on the surface of iron oxide (Fe3O4) nanotemplates is employed to tune the diameter and interdistance of RGD-bearing AuNPs at the receptor-level. The Fe3O4 nanotemplates decorated with RGD-bearing AuNPs arranged in various RGD diameters and interdistances at the receptor-levels are flexibly fastened to a substrate. Similar to fully connected RGDs, subreceptor-level-gapped (quasiconnected) RGDs activate integrin binding with the adjacent RGDs, which stimulates focal adhesion, mechanosensing, and differentiation of stem cells. This stimulation of stem cells is hindered when the RGD interdistance increases above the receptor-level gap. However, this stimulation is partially effective when the RGD diameter also increases far above the receptor-level gap. Strikingly, magnetically attracted fastening of the RGDs toward the substrate via polymer linker tightening fully stimulates adhesion and differentiation of stem cells in a reversible manner, both in vitro and in vivo. Various RGD diameter and interdistance on Fe3O4 nanotemplates can further elucidate the dynamic receptor-level RGD proximity-regulated stem cell differentiation that govern tissue repair.

Original languageEnglish
Article number2200828
JournalAdvanced Functional Materials
Volume32
Issue number30
DOIs
Publication statusPublished - 2022 Jul 25

Bibliographical note

Funding Information:
G.B. and M.S.K. contributed equally to this work. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (Nos. 2020R1C1C1011038 and 2019R1A2C3006587). This work was also supported by a Korea University Grant. HAADF‐STEM imaging was conducted with the support of the Seoul center in Korea Basic Science Institute (KBSI). The surgery was conducted after being approved by the Institutional Animal Care and Use Committee of Korea University.

Funding Information:
G.B. and M.S.K. contributed equally to this work. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (Nos. 2020R1C1C1011038 and 2019R1A2C3006587). This work was also supported by a Korea University Grant. HAADF-STEM imaging was conducted with the support of the Seoul center in Korea Basic Science Institute (KBSI). The surgery was conducted after being approved by the Institutional Animal Care and Use Committee of Korea University.

Publisher Copyright:
© 2022 Wiley-VCH GmbH.

Keywords

  • integrin clustering
  • ligand fastening
  • ligand proximity
  • stem cell adhesion
  • stem cell differentiation

ASJC Scopus subject areas

  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics

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