Institute of Biomedical Engineering and Health Sciences, College of Pharmaceutical Engineering and Life Science, Changzhou University, 1 Gehu Road, Wujin District, Changzhou City, Jiangsu Province, 213164, China.
Institute of Biomedical Engineering and Health Sciences, College of Pharmaceutical Engineering and Life Science, Changzhou University, 1 Gehu Road, Wujin District, Changzhou City, Jiangsu Province, 213164, China.
Biochem Biophys Res Commun. 2020 Apr 2;524(2):317-324. doi: 10.1016/j.bbrc.2020.01.019. Epub 2020 Jan 26.
Extracellular Matrix (ECM) assembly and remodeling are critical physiological events in vivo, and abnormal ECM assembly or remodeling is related to pathological conditions such as osteoarthritis, fibrosis, cancers, and genetic diseases. ECM assembly/remodeling driven by cells represents more physiological processes. Collagen I (COL) is very abundant in tissues, which assembly/remodeling is mediated by biochemical and mechanical factors. How cells regulate COL assembly biomechanically still remains to be well understood. Here we used fluorescent COL in the medium to study how cells assembled ECM which represents more physiological structures. The results showed that MDCK cells actively recruited COL from the medium and helped assemble the fibers, which in turn facilitated cell branching morphogenesis, both displaying highly spatial associations and mutual dependency. Inhibition of cellular contraction force by ROCK and Myosin II inhibitors attenuated but did not block the COL fiber formation, while cell motion showed high consistency with the fiber assembly. Under ROCK or Myosin II inhibition, further analysis indicated high correlation between local cell movement and COL fiber strength as quantified from different regions of the same groups. Blocking cell motion by actin cytoskeleton disruption completely inhibited the fiber formation. These suggest that cell motion coordinated COL fiber assembly from the medium, possibly through generated strain on deposited COL to facilitate the fiber growth.
细胞外基质（ECM）的组装和重塑是体内关键的生理事件，异常的 ECM 组装或重塑与骨关节炎、纤维化、癌症和遗传疾病等病理状况有关。细胞驱动的 ECM 组装/重塑代表了更多的生理过程。I 型胶原（COL）在组织中非常丰富，其组装/重塑受生化和机械因素的调节。细胞如何通过生物力学调节 COL 的组装仍然知之甚少。在这里，我们使用荧光 COL 培养基来研究细胞如何组装代表更生理结构的 ECM。结果表明，MDCK 细胞从培养基中积极募集 COL 并帮助组装纤维，这反过来又促进了细胞分支形态发生，两者都显示出高度的空间关联和相互依赖性。ROCK 和肌球蛋白 II 抑制剂抑制细胞收缩力会减弱但不会阻断 COL 纤维的形成，而细胞运动与纤维组装具有高度一致性。在 ROCK 或肌球蛋白 II 抑制下，进一步的分析表明，在同一组的不同区域定量时，局部细胞运动与 COL 纤维强度之间存在高度相关性。通过破坏肌动蛋白细胞骨架阻止细胞运动完全抑制了纤维的形成。这些表明细胞运动从培养基中协调 COL 纤维组装，可能通过在沉积的 COL 上产生应变来促进纤维生长。
