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Effects of Morphology vs. Cell–Cell Interactions on Endothelial Cell Stiffness

机译:形态学的影响和。细胞间相互作用对内皮细胞刚度的影响

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Biological processes such as atherogenesis, wound healing, cancer cell metastasis, and immune cell transmigration rely on a delicate balance between cell–cell and cell–substrate adhesion. Cell mechanics have been shown to depend on substrate factors such as stiffness and ligand presentation, while the effects of cell–cell interactions on the mechanical properties of cells has received little attention. Here, we use atomic force microscopy to measure the Young’s modulus of live human umbilical vein endothelial cells (HUVECs). In varying the degree of cell–cell contact in HUVECs (single cells, groups, and monolayers), we observe that increased cell stiffness correlates with an increase in cell area. Further, we observe that HUVECs stiffen as they spread onto a glass substrate. When we weaken cell–cell junctions (i.e., through a low dose of cytochalasin B or treatment with a VE-cadherin antibody), we observe that cell–substrate adhesion increases, as measured by focal adhesion size and density, and the stiffness of cells within the monolayer approaches that of single cells. Our results suggest that while morphology can roughly be used to predict cell stiffness, cell–cell interactions may play a significant role in determining the mechanical properties of individual cells in tissues by careful maintenance of cell tension homeostasis.
机译:动脉粥样硬化,伤口愈合,癌细胞转移和免疫细胞迁移等生物学过程依赖于细胞与细胞和细胞与基质之间的粘附力之间的微妙平衡。已经证明细胞力学依赖于底物因素,例如刚度和配体的表现,而细胞间相互作用对细胞机械性能的影响却很少引起关注。在这里,我们使用原子力显微镜来测量活人脐静脉内皮细胞(HUVEC)的杨氏模量。通过改变HUVEC(单细胞,组和单层)中的细胞间接触程度,我们观察到细胞刚度增加与细胞面积增加相关。此外,我们观察到HUVEC在扩散到玻璃基板上时会变硬。当我们减弱细胞-细胞连接时(即通过低剂量的细胞松弛素B或VE-钙粘蛋白抗体处理),我们观察到细胞-基质的粘附力增加,这是通过粘着斑大小和密度以及细胞的硬度来衡量的单层内的细胞接近单细胞的细胞。我们的结果表明,虽然形态学可以粗略地用来预测细胞的刚度,但细胞与细胞之间的相互作用可能通过谨慎地维持细胞张力的动态平衡而在确定组织中单个细胞的机械特性方面发挥重要作用。

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