3D matrix stiffness modulation unveils cardiac fibroblast phenotypic switching

作者：Yan Han, Yan Han, Zehua Shao, Yuanhao Zhang, Huan Zhao, Zirui Sun, Hao Tang, Hao Tang, Yu Han, Yu Han, Chuanyu Gao · 发表于：Scientific Reports · 年份：2024 · DOI：10.1038/s41598-024-67646-x · 被引用次数：22 · 研究领域：Cellular Mechanics and Interactions、Tissue Engineering and Regenerative Medicine、Elasticity and Material Modeling

This study investigates how dynamic fluctuations in matrix stiffness affect the behavior of cardiac fibroblasts (CFs) within a three-dimensional (3D) hydrogel environment. Using hybrid hydrogels with tunable stiffness, we created an in vitro model to mimic the varying stiffness of the cardiac microenvironment. By manipulating hydrogel stiffness, we examined CF responses, particularly the expression of α-smooth muscle actin (α-SMA), a marker of myofibroblast differentiation. Our findings reveal that increased matrix stiffness promotes the differentiation of CFs into myofibroblasts, while matrix softening reverses this process. Additionally, we identified the role of focal adhesions and integrin β1 in mediating stiffness-induced phenotypic switching. This study provides significant insights into the mechanobiology of cardiac fibrosis and suggests that modulating matrix stiffness could be a potential therapeutic strategy for treating cardiovascular diseases.