Kim Chowon, Kang Nayeon, Min Sunhong, Thangam Ramar, Lee Sungkyu, Hong Hyunsik, Kim Kanghyeon, Kim Seong Yeol, Kim Dahee, Rha Hyunji, Tag Kyong-Ryol, Lee Hyun-Jeong, Singh Nem, Jeong Daun, Hwang Jangsun, Kim Yuri, Park Sangwoo, Lee Hyesung, Kim Taeeon, Son Sang Wook, Park Steve, Karamikamkar Solmaz, Zhu Yangzhi, Hassani Najafabadi Alireza, Chu Zhiqin, Sun Wujin, Zhao Pengchao, Zhang Kunyu, Bian Liming, Song Hyun-Cheol, Park Sung-Gyu, Kim Jong Seung, Lee Sang-Yup, Ahn Jae-Pyoung, Kim Hong-Kyu, Zhang Yu Shrike, Kang Heemin
Department of Materials Science and Engineering, Korea University, Seoul, Republic of Korea.
Advanced Analysis Center, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
Nat Commun. 2024 Dec 23;15(1):10665. doi: 10.1038/s41467-024-54557-8.
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.
天然细胞外基质不断重塑，形成复杂的相互连接的网络结构，可逆地调节干细胞行为。对其复杂动态性的调控和理解有助于调节多种细胞行为。然而，由于缺乏对具有动态可控性的此类复杂结构的设计和建模，这两点尚未实现。在此，我们报告了使用图论对模拟细胞外基质的配体簇间连接进行基于模块化的数学建模。磁性纳米阻滞剂各向异性的增加会按比例断开精氨酸 - 甘氨酸 - 天冬氨酸配体与配体之间的连接，并减少配体簇间边缘的数量。这种现象会使干细胞失活，而通过使纳米阻滞剂线性化可部分激活干细胞。高各向异性纳米阻滞剂的远程循环升高会在纳米阻滞剂下方灵活产生纳米间隙，并增加配体簇间边缘的数量。随后，刺激了整合素表达的干细胞浸润，这在体外和体内均可逆地增强了粘着斑和机械转导驱动的分化。设计和系统建模细胞外基质模拟几何形状为揭示用于组织再生的动态细胞 - 材料相互作用开辟了途径。
