Magnetic Control of Multiscale Ligand Nanoarchitecture Regulates Stem Cell Fate
Abstract Native tissues exhibit hierarchical structures of anisotropically arranged extracellular matrix that dynamically regulate stem cells and tissue function. However, neither multiscale nano‐anisotropy nor dynamic anisotropy control have been reported. In this study, spherical or rod‐shaped gold small‐nanomaterials (at integrin receptor‐scale; tens of nanometers) are coupled to the surface of spherical or rod‐shaped magnetic large‐nanomaterials (at focal adhesion complex‐scale; hundreds of nanometers), with both showing constant surface areas at each respective scale. Each hierarchical nanocomposite is flexibly conjugated to the substrate material surface at constant densities, resulting in dual‐scale liganded nano‐anisotropies. Increasing the aspect ratio of liganded nanomaterials at the hundreds of nanometer‐scale dominantly promotes integrin recruitment, focal adhesion, mechanotransduction, and differentiation of stem cells over that at the tens of nanometer‐scale. Such scale‐specific liganded nano‐anisotropy effects on stem cell regulation are temporally regulated both in vitro and in vivo by physically raising or lowering hierarchical nanocomposites to respectively inhibit or stimulate stem cell adhesion and differentiation on curved surfaces by modulating cell membrane bending. Such unprecedented “dynamic dual‐scale ligand anisotropy” can be independently engineered regarding material scales, anisotropies, and ligands to elucidate scale‐specific dynamic cell‐material interactions and allow for multimodal stem cell regulation to enhance tissue‐regenerative therapy.
Authors
- Jeongyun Heo (ORCID: https://orcid.org/0000-0002-0507-9358)
- Alireza Hassani Najafabadi (ORCID: https://orcid.org/0000-0002-8215-4374)
- Chowon Kim
- Sang Kyu Kwak (ORCID: https://orcid.org/0000-0002-0332-1534)
- Kyong‐Ryol Tag
- Nayeon Kang (ORCID: https://orcid.org/0009-0003-3805-6675)
- Sang Wook Son (ORCID: https://orcid.org/0000-0002-3332-7056)
- Ramar Thangam (ORCID: https://orcid.org/0000-0002-6209-7149)
- Kanghyeon Kim
- Jae‐Pyoung Ahn (ORCID: https://orcid.org/0000-0003-2657-7425)
- Jang‐Kyoo Shin (ORCID: https://orcid.org/0000-0002-0469-1676)
- Hyun‐Jeong Lee
- Hyun‐Do Jung (ORCID: https://orcid.org/0000-0001-8632-7431)
- Juyoung Yoon (ORCID: https://orcid.org/0000-0002-1728-3970)
- Hyun‐Cheol Song (ORCID: https://orcid.org/0000-0001-5563-9088)
- Yu Shrike Zhang (ORCID: https://orcid.org/0000-0002-0045-0808)
- Hyunsik Hong (ORCID: https://orcid.org/0000-0003-0823-3119)
- Guosheng Song (ORCID: https://orcid.org/0000-0001-5628-6245)
- Iman Zare (ORCID: https://orcid.org/0000-0002-0056-5576)
- Heemin Kang (ORCID: https://orcid.org/0000-0003-2694-9882)
- Sehoon Kim (ORCID: https://orcid.org/0000-0002-8074-1006)
- Jong Seung Kim (ORCID: https://orcid.org/0000-0003-3477-1172)
- Hong‐Kyu Kim (ORCID: https://orcid.org/0000-0001-9723-2382)
- Hwapyung Jung (ORCID: https://orcid.org/0000-0002-9990-0660)
- Yumi Cho (ORCID: https://orcid.org/0000-0003-3296-5619)
- Hyoung Kyun Rha
Institutions
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Ewha Womans University (KR)
- Korea Advanced Institute of Science and Technology (KR)
- Hunan University (CN)
- Korea University (KR)
- Ansan University (KR)
- Terasaki Foundation (US)
- State Key Laboratory of Chemobiosensing and Chemometrics (CN)
- Hanyang University (KR)
- Ulsan National Institute of Science and Technology (KR)
- Korea Institute of Science and Technology (KR)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- Advanced Functional Materials
- Published
- 2025-03-26
- DOI
- https://doi.org/10.1002/adfm.202422618
- Citations
- 5
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 5.76
Funders
- National Research Foundation of Korea