Li Jing, Chen Huarong, Xu Yue, Hu Jiliang, Xie Fu Qiang, Yang Chun
Institute of Biomechanics and Medical Engineering, School of Aerospace Engineering,Tsinghua University, Beijing 100084, PR China.
Department of Stomatology, The Second Hospital of Lanzhou University, Lanzhou 730000, PR China.
J Biomech. 2016 Sep 6;49(13):2644-2654. doi: 10.1016/j.jbiomech.2016.05.024. Epub 2016 Jun 2.
Tissue mechanics provides an appropriate niche for cell growth and functions. Integrin proteins play a pivotal role in mechanosensing associated with both extracellular matrix and intracellular cytoskeleton proteins. Endocytosis of integrin β1 of BMMSCs on collagen I-coated soft substrates promotes cell differentiation, providing a mechanism that cell senses elasticity through integrin. To determine whether other integrin subunits act the same way in BMMSCs, we carried on immunocytochemical staining and biotin labeling experiments to assay their subcellular distribution on stiff and soft hydrogels. Our results indicate that, consistent with our previous studies conducted on β1 integrin, more integrin α1 and α2 were internalized on collagen I-coated soft substrates compared with stiff substrate counterparts. This internalization is mainly mediated by caveolin-dependent endocytosis and would involve in soft matrix-promoted neurogentic lineage commitment. Cells on hydrogels coated by fibronectin and laminin, respective ligands of integrin α5 and α6, demonstrated no apparent soft substrate inducing endocytosis of these two subunits. These findings suggest that integrin-mediated mechanosensing is coupling with ECM ligands.
组织力学为细胞生长和功能提供了适宜的微环境。整合素蛋白在与细胞外基质和细胞内细胞骨架蛋白相关的机械传感中起关键作用。骨髓间充质干细胞的整合素β1在包被有I型胶原的软基质上的内吞作用促进细胞分化，这提供了一种细胞通过整合素感知弹性的机制。为了确定其他整合素亚基在骨髓间充质干细胞中是否也有相同作用，我们进行了免疫细胞化学染色和生物素标记实验，以检测它们在硬水凝胶和软水凝胶上的亚细胞分布。我们的结果表明，与我们之前对β1整合素的研究一致，与硬基质相比，更多的整合素α1和α2在包被有I型胶原的软基质上发生内化。这种内化主要由小窝蛋白依赖的内吞作用介导，并参与软基质促进的神经发生谱系定向分化。在分别被整合素α5和α6的配体纤连蛋白和层粘连蛋白包被的水凝胶上的细胞，未表现出明显的软基质诱导这两个亚基的内吞作用。这些发现表明整合素介导的机械传感与细胞外基质配体相关联。
