Effect of substrate stiffness on hepatocyte migration and cellular Young's modulus
Effect of substrate stiffness on hepatocyte migration and cellular Young's modulus
复制标题
基质硬度对肝细胞迁移和细胞杨氏模量的影响
DOI：
10.1002/jcp.26491
复制
发表时间：
2018-09-01
影响因子：
5.6
通讯作者：
Yang，Li
中科院分区：
文献类型：
--
作者：
Xia，Tingting;Zhao，Runze;Yang，Li
肝纤维化的进展伴随着细胞外基质（ECM）的不平衡降解和沉积，导致组织硬度增加。肝细胞与肝脏内的所有肝内细胞群相互作用。然而，肝细胞迁移和细胞的杨氏模量如何受到基板刚度的影响还没有很好地理解。在这里，我们通过使用聚乙烯醇（PVA）水凝胶建立了刚度可控的体外细胞培养模型，该水凝胶模拟了与纤维化肝脏相同的物理刚度。在我们的实验中使用了三个硬度水平，其对应于在正常肝组织（4.5kPa）、纤维化肝组织的早期（19 kPa）和晚期（37 kPa）中发现的硬度水平。肝细胞骨架受基质硬度的影响。软质基质促进细胞的迁移和定向性。随着基底刚度的增加，蜂窝状材料的杨氏模量先增大后减小。细胞膜上整合素-β1和β-连环素的表达分别随着底物硬度的增加而上调和下调。我们的数据不仅表明肝细胞对基质刚度敏感，而且还表明基质刚度，细胞杨氏模量和整合素-β1和β-连环蛋白途径的动态平衡之间可能存在潜在的关系。这些结果可能为机械依赖性疾病，特别是纤维化相关疾病的机制研究提供新的见解。
Hepatic fibrosis progress accompanied by an unbalanced extracellular matrix (ECM) degradation and deposition leads to an increased tissue stiffness. Hepatocytes interplay with all intrahepatic cell populations inside the liver. However, how hepatocytes migration and cellular Young's modulus influenced by the substrate stiffness are not well understood. Here, we established a stiffness‐controllable in vitro cell culture model by using a polyvinyl alcohol (PVA) hydrogel that mimicked the same physical stiffness as a fibrotic liver. Three levels of stiffness were used in our experiment that corresponded to the stiffness levels found in normal liver tissue (4.5 kPa), the early (19 kPa) and late stages (37 kPa) of fibrotic liver tissues. Cytoskeleton of hepatocyte was influenced by substrate stiffness. Soft substrate promoted the cellular migration and directionality. The cellular Young's modulus firstly increased and then decreased with increasing substrate stiffness. Integrin‐β1 and β‐catenin expression on cytomembrane were up‐regulated and down‐regulated with the increase of substrate stiffness, respectively. Our data not only suggested that hepatocytes were sensitive to substrate stiffness, but also suggested that there may be a potential relationship among substrate stiffness, cellular Young's modulus and the dynamic balance of integrin‐β1 and β‐catenin pathways. These results may provide us a new insight in mechanism investigation of mechano‐dependent diseases, especially like fibrosis related diseases.