Chiral geometry regulates stem cell fate and activity
Chiral geometry regulates stem cell fate and activity
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手性几何形状调节干细胞的命运和活性
DOI：
10.1016/j.biomaterials.2019.119456
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发表时间：
2019-11-01
期刊：
影响因子：
14
通讯作者：
Yu, Mengfei
中科院分区：
文献类型：
--
作者：
Dong, Lingqing;Gong, Jiaxing;Yu, Mengfei
细胞的几何结构感测不可避免地涉及细胞骨架重塑和生化信号的激活，其控制细胞行为的多个方面，例如增殖、分化和迁移。各种大小，形状和几何形状依赖的细胞行为已被揭示，但几何手性的作用，在调节，细胞行为和潜在的生物物理机制仍然难以捉摸。在这里，我们报告了一个有趣的机械转导的干细胞的手性几何形状，人骨髓间充质干细胞（hMSCs）更喜欢向右旋几何迁移，近30%的相对优势，迁移速度，被称为“chirotaxis”。我们还发现，细胞的粘附，增殖和分化的hMSCs培养在右侧几何大大增强比那些在左侧几何，通过触发转录因子AP-1复合物通过p38/MAPK信号调节hMSCs的命运和活动。我们证明了由横向和径向应力纤维组成的细胞骨架网络通过粘着斑对右旋/左旋几何结构具有增强/抵消作用，因此，细胞的细胞骨架收缩性在右旋几何结构上高出近80%。这些发现强调了几何手性作为细胞外信号通过细胞-物质相互作用调节干细胞行为的重要性。
Geometry sensing of cells inevitably involves cytoskeletal remodeling and the activation of biochemical signaling, which control multiple aspects of cell behaviors, such as proliferation, differentiation and migration.,A variety of size-, shape, and geometry-dependent cell behaviors have been revealed, but the role of geometric chirality in regulating, cellular behaviors and the underlying biophysical mechanisms remain elusive. Here, we report an intriguing mechanotransduction of stem cells on chiral geometries that human mesenchymal stem cells (hMSCs) prefer to migrate towards dextral geometry with nearly 30% relative advantage in migration speed, referred to as "chirotaxis". We also found that cell adhesion, proliferation, and differentiation of hMSCs are greatly enhanced for cells cultured on dextral geometry than those On sinistral geometry, by triggering tran: scription factor AP-1 complex through p38/MAPK signaling that regulates hMSCs fate and activity. We demonstrated that the cytoskeletal network consisting of transverse and radial stress fibers exhibits a strengthening/offsetting effect on dextral/sinistral geometry through focal adhesion sites, and consequently, cell's cytoskeletal contractility on the dextral geometry is nearly 80% higher. These findings highlight the importance of geometric chirality as an extracellular cue in regulating stem cell's behaviors through cell-material interactions.