Reversible Tuning of Multiple Molecular Kinking for Stem Cell Regulation In Vivo
ABSTRACT In the native extracellular matrix, collagen fibrils regulate stem cell fate and tissue regeneration by modulating the number of serial kinks via intramolecular kinking and unkinking, which affects integrin ligation. However, biomimetic materials composed solely of multi‐kink‐bearing molecules for dynamic regulation of ligand exposure remain limited. In this study, we designed materials composed solely of liganded multiple kink‐bearing molecules with a tunable number of kink points (mono‐kink, tri‐kink, and penta‐kink molecules), including flexible linkers and densely packed via intermolecular interactions, are designed. Near‐infrared‐upconverted ultraviolet light and visible light induce multiple kinking and unkinking of liganded multiple kink‐bearing molecules conjugated to upconversion nanoparticle‐coated materials, inducing kinked and unkinked states, respectively. Tri‐kinking and unkinking mediate the effective regulation of ligand masking and exposure, respectively, by modulating intermolecular interactions, while mono‐kink and penta‐kink molecules continuously expose the ligands regardless of their kinking/unkinking state. Tri‐unkinking cyclically stimulates integrin ligation and focal adhesion‐mediated stem cell mechanotransduction and differentiation in vivo, which are inhibited by tri‐kinking. This study presents a newly developed reversibly switchable multi‐kink molecule‐conjugated surface for dynamic regulation of ligand exposure and stem cell responses, providing a useful modality for regulating cell–material interactions and stem cell fate in vivo.
Authors
- Rongqin Huang (ORCID: https://orcid.org/0000-0002-1126-4226)
- Jeongyun Heo (ORCID: https://orcid.org/0000-0002-0507-9358)
- Dahee Kim (ORCID: https://orcid.org/0000-0001-7286-1334)
- Chowon Kim
- Ji Hye Choi (ORCID: https://orcid.org/0000-0002-0062-4222)
- Nayeon Kang (ORCID: https://orcid.org/0009-0003-3805-6675)
- Ramar Thangam (ORCID: https://orcid.org/0000-0002-6209-7149)
- Kanghyeon Kim
- Taehoon Ha (ORCID: https://orcid.org/0000-0002-4533-1140)
- Hyun‐Do Jung (ORCID: https://orcid.org/0000-0001-8632-7431)
- Sunghoon Hur (ORCID: https://orcid.org/0000-0001-6985-5937)
- Pooyan Makvandi (ORCID: https://orcid.org/0000-0003-2456-0961)
- Jeongah Shin
- Cheol Hwan Kwak (ORCID: https://orcid.org/0000-0003-3034-9775)
- Hyun‐Cheol Song (ORCID: https://orcid.org/0000-0001-5563-9088)
- Yun Suk Huh (ORCID: https://orcid.org/0000-0003-1612-4473)
- Jangsun Hwang (ORCID: https://orcid.org/0000-0001-5814-3467)
- Hyunsik Hong (ORCID: https://orcid.org/0000-0003-0823-3119)
- Sungkyu Lee (ORCID: https://orcid.org/0000-0002-6419-2086)
- Heemin Kang (ORCID: https://orcid.org/0000-0003-2694-9882)
- Wenguo Cui (ORCID: https://orcid.org/0000-0002-6938-9582)
- Honghwan Choi (ORCID: https://orcid.org/0000-0001-7308-9438)
- Sehoon Kim (ORCID: https://orcid.org/0000-0002-8074-1006)
- Rasoul Moradi (ORCID: https://orcid.org/0000-0001-8652-9738)
- Min Jae Lee (ORCID: https://orcid.org/0000-0002-3252-6467)
- Yuri Kim (ORCID: https://orcid.org/0000-0002-9385-2557)
- Daun Jeong (ORCID: https://orcid.org/0000-0003-0769-9697)
- Jungyeon Rhi
- Choongmo Kang
Institutions
- Khazar University (AZ)
- Ewha Womans University (KR)
- Seoul National University (KR)
- University of California, Los Angeles (US)
- Inha University (KR)
- Korea University (KR)
- Ruijin Hospital (CN)
- Integrative Medicine Institute (US)
- Samueli Institute (US)
- Henan Cancer Hospital (CN)
- Korea University (JP)
- Hanyang University (KR)
- Hyundai Motors (South Korea) (KR)
- Korea Institute of Science and Technology (KR)
- Chitkara University (IN)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- Advanced Functional Materials
- Published
- 2026-09-14
- DOI
- https://doi.org/10.1002/adfm.77914
- Primary Topic
- Cell Adhesion Molecules Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00