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Abstract：
The dynamic nature of the extracellular matrix (ECM), particularly its stiffness, plays a pivotal role in cellular behavior, especially after myocardial infarction (MI), where cardiac fibroblasts (cFbs) are key in ECM remodeling. This study explores the effects of dynamic stiffness changes on cFb activation and ECM production, addressing a gap in understanding the dynamics of ECM stiffness and their impact on cellular behavior. Utilizing gelatin methacrylate (GelMA) hydrogels, we developed a model to dynamically alter the stiffness of cFb environment through a two-step photocrosslinking process. By inducing a quiescent state in cFbs with a TGF-β inhibitor, we ensured the direct observation of cFbs-responses to the engineered mechanical environment. Our findings demonstrate that the mechanical history of substrates significantly influences cFb activation and ECM-related gene expression. Cells that were initially cultured for 24 h on the soft substrate remained more quiescent when the hydrogel was stiffened compared to cells cultured directly to a stiff static substrate. This underscores the importance of past mechanical history in cellular behavior. The present study offers new insights into the role of ECM stiffness changes in regulating cellular behavior, with significant implications for understanding tissue remodeling processes, such as in post-MI scenarios.
摘要：
细胞外基质（ECM）的动态性质，特别是它的刚度，在细胞行为中起着关键作用，尤其是心肌梗死（MI）后，其中心脏成纤维细胞（cFbs）是ECM重塑的关键。本研究探讨了动态刚度变化对CFB活化和ECM产生的影响，解决了理解ECM刚度动力学及其对细胞行为影响的差距。利用明胶甲基丙烯酸酯（GelMA）水凝胶，我们开发了一个模型，通过两步光交联过程动态改变cfb环境的刚度。通过用TGF-β抑制剂在cFbs中诱导静止状态，我们确保了对工程机械环境的cFbs响应的直接观察。我们的发现表明，底物的机械历史显着影响cFb激活和ECM相关基因表达。与直接培养到刚性静态基质的细胞相比,当水凝胶变硬时,最初在软基质上培养24小时的细胞保持更静止。这强调了过去的机械历史在细胞行为中的重要性。本研究为ECM刚度变化在调节细胞行为中的作用提供了新的见解，对理解组织重塑过程具有重要意义，例如在MI后场景中。
