Department of Chemical & Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles St, Baltimore, MD 21212, USA.
J Biol Eng. 2009 Jul 8;3:10. doi: 10.1186/1754-1611-3-10.
Gradients of morphogens pattern cell fate - a phenomenon that is especially important during development. A simple model system for studying how morphogens pattern cell behavior would overcome difficulties inherent in the study of natural morphogens in vivo. A synthetic biology approach to building such a system is attractive.
Using an externally-tunable band-pass filter paradigm, we engineered Escherichia coli cells to function as a model system for the study of how multiple morphogens can pattern cell behavior. We demonstrate how our system exhibits behavior such as morphogen crosstalk and how the cells' growth and fluorescence can be patterned in a number of complex patterns. We extend our cell patterning from 2D cultures on the surface of plates to 3D cultures in soft agarose medium.
Our system offers a convenient, well-defined model system for fundamental studies on how multiple morphogen gradients can affect cell fate and lead to pattern formation. Our design principles could be applied to eukaryotic cells to develop other models systems for studying development or for enabling the patterning of cells for applications such as tissue engineering and biomaterials.
形态发生梯度决定细胞命运——这一现象在发育过程中尤为重要。研究形态发生如何影响细胞行为的简单模型系统将克服在体内研究天然形态发生物固有存在的困难。利用合成生物学方法构建这样的系统具有吸引力。
我们使用可外部调节的带通滤波器范例，将大肠杆菌细胞设计为研究多种形态发生物如何影响细胞行为的模型系统。我们展示了我们的系统如何表现出形态发生物交叉对话的行为，以及细胞的生长和荧光如何在许多复杂模式中被模式化。我们将细胞图案化从平板表面的 2D 培养扩展到琼脂糖软培养基中的 3D 培养。
我们的系统为研究多个形态发生梯度如何影响细胞命运并导致图案形成的基本研究提供了一个方便、定义明确的模型系统。我们的设计原则可以应用于真核细胞，以开发用于研究发育或用于为组织工程和生物材料等应用进行细胞图案化的其他模型系统。
