Harati Javad, Du Ping, Galluzzi Massimiliano, Li Xian, Lin Jiao, Pan Haobo, Wang Peng-Yuan
Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
University of Chinese Academy of Science, Beijing 101408, China.
ACS Appl Mater Interfaces. 2024 Jul 17;16(28):35912-35924. doi: 10.1021/acsami.4c02989. Epub 2024 Jul 8.
The extracellular matrix (ECM) shapes the stem cell fate during differentiation by exerting relevant biophysical cues. However, the mechanism of stem cell fate decisions in response to ECM-backed complex biophysical cues has not been fully understood due to the lack of versatile ECMs. Here, we designed two versatile ECMs using colloidal self-assembly technology to probe the mechanisms of their effects on mechanotransduction and stem cell fate regulation. Binary colloidal crystals (BCC) with a hexagonally close-packed structure, composed of silica (5 μm) and polystyrene (0.4 μm) particles as well as a polydimethylsiloxane-embedded BCC (BCCP), were fabricated. They have defined surface chemistry, roughness, stiffness, ion release, and protein adsorption properties, which can modulate the cell adhesion, proliferation, and differentiation of human adipose-derived stem cells (hASCs). On the BCC, hASCs preferred osteogenesis at an early stage but showed a higher tendency toward adipogenesis at later stages. In contrast, the results of BCCP diverged from those of BCC, suggesting a unique regulation of ECM-dependent mechanotransduction. The BCC-mediated cell adhesion reduced the size of the focal adhesion complex, accompanying an ordered spatial organization and cytoskeletal rearrangement. This morphological restriction led to the modulation of mechanosensitive transcription factors, such as c-FOS, the enrichment of transcripts in specific signaling pathways such as PI3K/AKT, and the activation of the Hippo signaling pathway. Epigenetic analyses showed changes in histone modifications across different substrates, suggesting that chromatin remodeling participated in BCC-mediated mechanotransduction. This study demonstrates that BCCs are versatile artificial ECMs that can regulate human stem cells' fate through unique biological signaling, which is beneficial in biomaterial design and stem cell engineering.
细胞外基质（ECM）通过施加相关生物物理信号在分化过程中塑造干细胞命运。然而，由于缺乏通用的细胞外基质，干细胞对细胞外基质支持的复杂生物物理信号做出命运决定的机制尚未完全了解。在这里，我们使用胶体自组装技术设计了两种通用的细胞外基质，以探究它们对机械转导和干细胞命运调控的影响机制。制备了由二氧化硅（5μm）和聚苯乙烯（0.4μm）颗粒组成的具有六方密堆积结构的二元胶体晶体（BCC）以及嵌入聚二甲基硅氧烷的BCC（BCCP）。它们具有明确的表面化学、粗糙度、硬度、离子释放和蛋白质吸附特性，可调节人脂肪来源干细胞（hASC）的细胞粘附、增殖和分化。在BCC上，hASC在早期阶段倾向于成骨，但在后期阶段显示出更高的成脂倾向。相比之下，BCCP的结果与BCC不同，表明细胞外基质依赖性机械转导具有独特的调节作用。BCC介导的细胞粘附减小了粘着斑复合体的大小，伴随着有序的空间组织和细胞骨架重排。这种形态限制导致了机械敏感转录因子如c-FOS的调节、特定信号通路如PI3K/AKT中转录本的富集以及Hippo信号通路的激活。表观遗传学分析显示不同底物上组蛋白修饰的变化，表明染色质重塑参与了BCC介导的机械转导。这项研究表明，BCC是通用的人工细胞外基质，可通过独特的生物信号调节人类干细胞的命运，这对生物材料设计和干细胞工程有益。
