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.

细胞微环境刚度的变化与血管的许多病理过程有关。基质硬度已被证明对血管内皮细胞 (VECs) 和血管平滑肌细胞 (VSMCs) 具有广泛的影响。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 的量级，这与天然血管组织的机械性能 (1​​0-100 kPa) 不匹配。在此，我们构建了刚度为 18-86 kPa 的水凝胶基质，以探索生理刚度对血管细胞的影响。我们的研究结果表明，随着生理范围内刚度的增加，VECs和VSMCs的细胞粘附和增殖行为显着增强。在柔软的基质上，VECs 表达更多的一氧化氮 (NO)，VSMC 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 底物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）显着高于 86 kPa 和 333 kPa 之间（VECs 中为 137 个，VSMCs 中为 172 个）。 ），表明在生理范围内刚度的小幅增加对血管细胞行为的影响更大。总体而言，我们的结果扩展了对刚度如何影响生理范围内血管细胞行为的探索。172 在 VSMCs 中），表明在生理范围内刚度的小幅增加对血管细胞行为的影响更大。总体而言，我们的结果扩展了对刚度如何影响生理范围内血管细胞行为的探索。172 在 VSMCs 中），表明在生理范围内刚度的小幅增加对血管细胞行为的影响更大。总体而言，我们的结果扩展了对刚度如何影响生理范围内血管细胞行为的探索。