Photonic control of ligand nanospacing in self-assembly regulates stem cell fate

Sungkyu Lee, Jounghyun Yoo, Gunhyu Bae, Ramar Thangam, Jeongyun Heo, Jung Yeon Park, Honghwan Choi, Chowon Kim, Jusung An, Jungryun Kim, Kwang Rok Mun, Seungyong Shin, Kunyu Zhang, Pengchao Zhao, Yuri Kim, Nayeon Kang, Seong Beom Han, Dahee Kim, Jiwon Yoon, Misun KangJihwan Kim, Letao Yang, Solmaz Karamikamkar, Jinjoo Kim, Yangzhi Zhu, Alireza Hassani Najafabadi, Guosheng Song, Dong Hwee Kim, Ki Bum Lee, Soong Ju Oh, Hyun Do Jung, Hyun Cheol Song, Woo Young Jang, Liming Bian, Zhiqin Chu, Juyoung Yoon, Jong Seung Kim, Yu Shrike Zhang, Yongju Kim, Ho Seong Jang, Sehoon Kim, Heemin Kang

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of “closely nanospaced” ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with “closely nanospaced” ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of “distantly nanospaced” ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Original languageEnglish
Pages (from-to)164-180
Number of pages17
JournalBioactive Materials
Publication statusPublished - 2024 Apr

Bibliographical note

Publisher Copyright:
© 2023 The Authors


  • Dynamic self-assembly
  • In vivo tracking
  • Ligand nanospacing
  • Stem cell adhesion
  • Stem cell fate

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biomedical Engineering


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