Sun Yupeng, Deng Ruijie, Ren Xiaojun, Zhang Kaixiang, Li Jinghong
Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.
ACS Appl Bio Mater. 2019 Jan 22;2(1):570-576. doi: 10.1021/acsabm.8b00712. Epub 2019 Jan 4.
Cellular microenvironment has played a critical role in cell behavior regulation, natural tissue formation, and development. Specifically, the stiffness of extracellular matrix (ECM) not only helps cells to maintain their morphology and location but also provides physical cues to regulate cellular functions. Nevertheless, it is still hard for conventional matrix materials to explore cell behaviors and functions under their physical microenvironments due to potential long-term cytotoxicity or unphysiological stiffness. Herein, a biocompatible stiffness-tunable 2D gelatin methacryloyl (GelMA) hydrogel matrix is fabricated to explore the influence of ECM stiffness on cell morphology as well as cellular gene expression. GelMA, as a derivative of gelatin, can not only serve as cell culture matrixes due to the existence of bioactive peptide sequences and biocompatibility, but also mimic the stiffness of native ECMs. As a result, the stiffness of GelMA matrix can regulate cytoskeleton assembly and cell morphology via mechanotransduction-related genetic pathways (RhoA/ROCK and PI3K/Rac1 signaling pathway). Therefore, the 2D GelMA hydrogel matrix with tunable stiffness can be regard as an alternative cellular matrix, and has a potential to reveal the fundamental principle of ECM defect-associated diseases.
细胞微环境在细胞行为调控、天然组织形成和发育过程中发挥着关键作用。具体而言，细胞外基质（ECM）的硬度不仅有助于细胞维持其形态和位置，还提供物理信号来调节细胞功能。然而，由于潜在的长期细胞毒性或非生理硬度，传统基质材料仍然难以探究细胞在其物理微环境下的行为和功能。在此，制备了一种具有生物相容性且刚度可调的二维甲基丙烯酰化明胶（GelMA）水凝胶基质，以探究ECM硬度对细胞形态以及细胞基因表达的影响。GelMA作为明胶的衍生物，由于存在生物活性肽序列和生物相容性，不仅可以用作细胞培养基质，还能模拟天然ECM的硬度。因此，GelMA基质的硬度可通过机械转导相关的遗传途径（RhoA/ROCK和PI3K/Rac1信号通路）调节细胞骨架组装和细胞形态。所以，具有可调硬度的二维GelMA水凝胶基质可被视为一种替代性细胞基质，并且有潜力揭示与ECM缺陷相关疾病的基本原理。
