MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
Colloids Surf B Biointerfaces. 2022 Jun;214:112483. doi: 10.1016/j.colsurfb.2022.112483. Epub 2022 Mar 26.
Changes in the stiffness of the cellular microenvironment are involved in many pathological processes of blood vessels. Substrate stiffness has been shown to have extensive effects on vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). However, the material stiffness of most previously reported in-vitro models is ranging from ~100 kPa to the magnitude of MPa, which does not match the mechanical properties of natural vascular tissue (10-100 kPa). Herein, we constructed hydrogel substrates with the stiffness of 18-86 kPa to explore the effect of physiological stiffness on vascular cells. Our findings show that, with the increase of stiffness at the physiological range, the cell adhesion and proliferation behaviors of VECs and VSMCs are significantly enhanced. On the soft substrate, VECs express more nitric oxide (NO), and VSMCs tend to maintain a healthy contraction phenotype. More importantly, we find that the number of differentially expressed genes in cells cultured between 18 kPa and 86 kPa substrates (560 in VECs, 243 in VSMCs) is significantly higher than that between 86 kPa and 333 kPa (137 in VECs, 172 in VSMCs), indicating that a small increase in stiffness within the physiological range have a higher impact on vascular cell behaviors. Overall, our results expanded the exploration of how stiffness affects the behavior of vascular cells at the physiological range.
细胞微环境的刚性变化与血管的许多病理过程有关。已有研究表明，基质刚性对血管内皮细胞（VECs）和血管平滑肌细胞（VSMCs）有广泛的影响。然而，大多数先前报道的体外模型的材料刚度范围从~100 kPa 到 MPa 量级，与天然血管组织的力学性能（10-100 kPa）不匹配。在此，我们构建了刚度为 18-86 kPa 的水凝胶基底，以探索生理刚度对血管细胞的影响。我们的研究结果表明，随着生理范围内刚性的增加，VECs 和 VSMCs 的细胞黏附和增殖行为明显增强。在软基底上，VECs 表达更多的一氧化氮（NO），VSMCs 倾向于保持健康的收缩表型。更重要的是，我们发现，在 18 kPa 和 86 kPa 基底之间培养的细胞中差异表达基因的数量（VECs 中为 560 个，VSMCs 中为 243 个）明显高于 86 kPa 和 333 kPa 之间（VECs 中为 137 个，VSMCs 中为 172 个），这表明生理范围内刚性的微小增加对血管细胞行为的影响更大。总的来说，我们的研究结果扩展了对生理范围内刚度如何影响血管细胞行为的探索。
