Modularity-based mathematical modeling of ligand inter-nanocluster connectivity for unraveling reversible stem cell regulation

IF 14.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
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
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引用次数: 0

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.

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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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