Modularity-based mathematical modeling of ligand inter-nanocluster connectivity for unraveling reversible stem cell regulation
The native extracellular matrix is continuously remodeled to form complex interconnected network structures that reversibly regulate stem cell behaviors. Both regulation and understanding of its intricate dynamicity can help to modulate numerous cell behaviors. However, neither of these has yet been achieved due to the lack of designing and modeling such complex structures with dynamic controllability. Here we report modularity-based mathematical modeling of extracellular matrix-emulating ligand inter-cluster connectivity using the graph theory. Increasing anisotropy of magnetic nano-blockers proportionately disconnects arginine-glycine-aspartic acid ligand-to-ligand interconnections and decreases the number of ligand inter-cluster edges. This phenomenon deactivates stem cells, which can be partly activated by linearizing the nano-blockers. Remote cyclic elevation of high-anisotropy nano-blockers flexibly generates nano-gaps under the nano-blockers and augments the number of ligand inter-cluster edges. Subsequently, integrin-presenting stem cell infiltration is stimulated, which reversibly intensifies focal adhesion and mechanotransduction-driven differentiation both in vitro and in vivo. Designing and systemically modeling extracellular matrix-mimetic geometries opens avenues for unraveling dynamic cell-material interactions for tissue regeneration.
Authors
- Wujin Sun (ORCID: https://orcid.org/0000-0002-3167-111X)
- Alireza Hassani Najafabadi (ORCID: https://orcid.org/0000-0002-8215-4374)
- Solmaz Karamikamkar (ORCID: https://orcid.org/0000-0002-6151-1539)
- Dahee Kim (ORCID: https://orcid.org/0000-0001-7286-1334)
- Chowon Kim
- 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)
- Zhiqin Chu (ORCID: https://orcid.org/0000-0003-4671-5434)
- Nem Singh (ORCID: https://orcid.org/0000-0003-2952-3385)
- Seong Yeol Kim (ORCID: https://orcid.org/0000-0002-7195-1861)
- Hyun‐Cheol Song (ORCID: https://orcid.org/0000-0001-5563-9088)
- T. H. Kim
- Yu Shrike Zhang (ORCID: https://orcid.org/0000-0002-0045-0808)
- Jangsun Hwang (ORCID: https://orcid.org/0000-0001-5814-3467)
- Hyunsik Hong (ORCID: https://orcid.org/0000-0003-0823-3119)
- Sunhong Min (ORCID: https://orcid.org/0000-0001-9897-146X)
- Liming Bian (ORCID: https://orcid.org/0000-0003-4739-0918)
- Kunyu Zhang (ORCID: https://orcid.org/0000-0003-2481-4781)
- Sungkyu Lee (ORCID: https://orcid.org/0000-0002-6419-2086)
- Heemin Kang (ORCID: https://orcid.org/0000-0003-2694-9882)
- Sung‐Gyu Park (ORCID: https://orcid.org/0000-0002-0580-3211)
- Yangzhi Zhu (ORCID: https://orcid.org/0000-0003-2920-3365)
- Steve Park (ORCID: https://orcid.org/0000-0002-1428-592X)
- Sang‐Yup Lee (ORCID: https://orcid.org/0000-0003-1348-0296)
- Yuri Kim (ORCID: https://orcid.org/0000-0002-8482-1644)
- Jong Seung Kim (ORCID: https://orcid.org/0000-0003-3477-1172)
- Hyesung Lee (ORCID: https://orcid.org/0000-0003-0253-3110)
- Pengchao Zhao (ORCID: https://orcid.org/0009-0002-6863-6016)
- Hong‐Kyu Kim (ORCID: https://orcid.org/0000-0001-9723-2382)
- Daun Jeong (ORCID: https://orcid.org/0000-0003-0769-9697)
- Hyun‐Jeong Lee (ORCID: https://orcid.org/0000-0002-0983-3696)
- Sangwoo Park (ORCID: https://orcid.org/0009-0008-4094-4053)
- Hyoung Kyun Rha
Institutions
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Korea Advanced Institute of Science and Technology (KR)
- Yonsei University (KR)
- Korea University (KR)
- Korea University Medical Center (KR)
- Terasaki Foundation (US)
- Korea Institute of Materials Science (KR)
- Korea University (JP)
- Korea Institute of Science and Technology (KR)
- Sungkyunkwan University (KR)
- Virginia Tech (US)
- University of Hong Kong (HK)
- South China University of Technology (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-23
- DOI
- https://doi.org/10.1038/s41467-024-54557-8
- Citations
- 20
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 6.52
Funders
- National Research Foundation
- Korea University
- National Research Foundation of Korea
- Ministry of Science and ICT, South Korea
- Brigham Research Institute