Nature Communications (Dec 2024)
Modularity-based mathematical modeling of ligand inter-nanocluster connectivity for unraveling reversible stem cell regulation
- Chowon Kim,
- Nayeon Kang,
- Sunhong Min,
- Ramar Thangam,
- Sungkyu Lee,
- Hyunsik Hong,
- Kanghyeon Kim,
- Seong Yeol Kim,
- Dahee Kim,
- Hyunji Rha,
- Kyong-Ryol Tag,
- Hyun-Jeong Lee,
- Nem Singh,
- Daun Jeong,
- Jangsun Hwang,
- Yuri Kim,
- Sangwoo Park,
- Hyesung Lee,
- Taeeon Kim,
- Sang Wook Son,
- Steve Park,
- Solmaz Karamikamkar,
- Yangzhi Zhu,
- Alireza Hassani Najafabadi,
- Zhiqin Chu,
- Wujin Sun,
- Pengchao Zhao,
- Kunyu Zhang,
- Liming Bian,
- Hyun-Cheol Song,
- Sung-Gyu Park,
- Jong Seung Kim,
- Sang-Yup Lee,
- Jae-Pyoung Ahn,
- Hong-Kyu Kim,
- Yu Shrike Zhang,
- Heemin Kang
Affiliations
- Chowon Kim
- Department of Materials Science and Engineering, Korea University
- Nayeon Kang
- Department of Materials Science and Engineering, Korea University
- Sunhong Min
- Department of Materials Science and Engineering, Korea University
- Ramar Thangam
- Department of Materials Science and Engineering, Korea University
- Sungkyu Lee
- Department of Materials Science and Engineering, Korea University
- Hyunsik Hong
- Department of Materials Science and Engineering, Korea University
- Kanghyeon Kim
- Department of Materials Science and Engineering, Korea University
- Seong Yeol Kim
- Department of Materials Science and Engineering, Korea University
- Dahee Kim
- Department of Materials Science and Engineering, Korea University
- Hyunji Rha
- Department of Materials Science and Engineering, Korea University
- Kyong-Ryol Tag
- Department of Materials Science and Engineering, Korea University
- Hyun-Jeong Lee
- Department of Materials Science and Engineering, Korea University
- Nem Singh
- Department of Materials Science and Engineering, Korea University
- Daun Jeong
- Department of Orthopedic Surgery, Korea University Anam Hospital
- Jangsun Hwang
- Department of Orthopedic Surgery, Korea University Anam Hospital
- Yuri Kim
- Department of Materials Science and Engineering, Korea University
- Sangwoo Park
- Department of Materials Science and Engineering, Korea University
- Hyesung Lee
- Department of Chemical and Biomolecular Engineering, Yonsei University
- Taeeon Kim
- Nano-Bio Convergence Department, Korea Institute of Materials Science (KIMS)
- Sang Wook Son
- Department of Dermatology, Korea University Ansan Hospital, Korea University College of Medicine
- Steve Park
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)
- Solmaz Karamikamkar
- Terasaki Institute for Biomedical Innovation
- Yangzhi Zhu
- Terasaki Institute for Biomedical Innovation
- Alireza Hassani Najafabadi
- Terasaki Institute for Biomedical Innovation
- Zhiqin Chu
- Department of Electrical and Electronic Engineering, Joint Appointment with School of Biomedical Sciences, The University of Hong Kong
- Wujin Sun
- Department of Biological Systems Engineering, Virginia Tech
- Pengchao Zhao
- School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology
- Kunyu Zhang
- School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology
- Liming Bian
- School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology
- Hyun-Cheol Song
- Electronic Materials Research Center, Korea Institute of Science and Technology (KIST)
- Sung-Gyu Park
- Nano-Bio Convergence Department, Korea Institute of Materials Science (KIMS)
- Jong Seung Kim
- Department of Chemistry, Korea University
- Sang-Yup Lee
- Nano-Bio Convergence Department, Korea Institute of Materials Science (KIMS)
- Jae-Pyoung Ahn
- Advanced Analysis Center, Korea Institute of Science and Technology (KIST)
- Hong-Kyu Kim
- Advanced Analysis Center, Korea Institute of Science and Technology (KIST)
- Yu Shrike Zhang
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital Harvard Medical School
- Heemin Kang
- Department of Materials Science and Engineering, Korea University
- DOI
- https://doi.org/10.1038/s41467-024-54557-8
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 22
Abstract
Abstract 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.
