Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Biomaterials. 2012 Nov;33(32):8040-6. doi: 10.1016/j.biomaterials.2012.07.013. Epub 2012 Aug 11.
Synthetic extracellular matrices provide a framework in which cells can be exposed to defined physical and biological cues. However no method exists to manipulate single cells within these matrices. It is desirable to develop such methods in order to understand fundamental principles of cell migration and define conditions that support or inhibit cell movement within these matrices. Here, we present a strategy for manipulating individual mammalian stem cells in defined synthetic hydrogels through selective optical activation of Rac, which is an intracellular signaling protein that plays a key role in cell migration. Photoactivated cell migration in synthetic hydrogels depended on mechanical and biological cues in the biomaterial. Real-time hydrogel photodegradation was employed to create geometrically defined channels and spaces in which cells could be photoactivated to migrate. Cell migration speed was significantly higher in the photo-etched channels and cells could easily change direction of movement compared to the bulk hydrogels.
合成细胞外基质为细胞提供了一个可以暴露在特定物理和生物信号下的框架。然而，目前还没有在这些基质中操纵单个细胞的方法。为了理解细胞迁移的基本原理，并确定在这些基质中支持或抑制细胞运动的条件，开发这样的方法是很有必要的。在这里，我们提出了一种通过选择性光激活 Rac 来操纵单个哺乳动物干细胞的策略，Rac 是一种细胞内信号蛋白，在细胞迁移中起着关键作用。在合成水凝胶中，光激活细胞迁移依赖于生物材料中的力学和生物学线索。我们采用实时水凝胶光降解的方法在其中创建具有特定几何形状的通道和空间，从而可以对细胞进行光激活，使其发生迁移。与大块水凝胶相比，在光蚀刻通道中细胞的迁移速度明显更高，并且可以很容易地改变运动方向。
