Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
Sci Rep. 2013;3:2425. doi: 10.1038/srep02425.
While stem cells can sense and respond to physical properties of their environment, the molecular aspects how physical information is translated into biochemical signals remain unknown. Here we show that human mesenchymal stem cells (hMSCs) harvest and assemble plasma fibronectin into their extracellular matrix (ECM) fibrils within 24 hours. hMSCs pro-actively pull on newly assembled fibronectin ECM fibrils, and the fibers are more stretched on rigid than on soft fibronectin-coated polyacrylamide gels. Culturing hMSCs on single stretched fibronectin fibers upregulates hMSC osteogenesis. Osteogenesis was increased when αvβ3 integrins were blocked on relaxed fibronectin fibers, and decreased when α5β1 integrins were blocked or when epidermal growth factor (EGF) receptor signaling was inhibited on stretched fibronectin fibers. This suggests that hMSCs utilize their own contractile forces to translate environmental cues into differential biochemical signals by stretching fibronectin fibrils. Mechanoregulation of fibronectin fibrils may thus serve as check point to regulate hMSC osteogenesis.
虽然干细胞可以感知和响应其环境的物理特性，但物理信息如何转化为生化信号的分子方面仍然未知。在这里，我们表明人类间充质干细胞（hMSCs）在 24 小时内将血浆纤维连接蛋白收集并组装到其细胞外基质（ECM）纤维中。hMSCs 主动拉动新组装的纤维连接蛋白 ECM 纤维，并且在刚性而非柔软的纤维连接蛋白涂覆的聚丙烯酰胺凝胶上纤维被拉伸得更厉害。在单个拉伸的纤维连接蛋白纤维上培养 hMSCs 可上调 hMSC 成骨作用。在松弛的纤维连接蛋白纤维上阻断αvβ3 整联蛋白时，成骨作用增加，而在拉伸的纤维连接蛋白纤维上阻断α5β1 整联蛋白或抑制表皮生长因子（EGF）受体信号传导时，成骨作用降低。这表明 hMSCs 通过拉伸纤维连接蛋白纤维利用自身的收缩力将环境线索转化为差异生化信号。因此，纤维连接蛋白纤维的机械调节可能作为调节 hMSC 成骨作用的检查点。
