Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Protein Sci. 2012 Jul;21(7):918-28. doi: 10.1002/pro.2089. Epub 2012 Jun 5.
Arguably, one of the foremost distinctions between life and non-living matter is the ability to sense environmental changes and respond appropriately--an ability that is invested in every living cell. Within a single cell, this function is largely carried out by networks of signaling molecules. However, the details of how signaling networks help cells make complicated decisions are still not clear. For instance, how do cells read graded, analog stress signals but convert them into digital live-or-die responses? The answer to such questions may originate from the fact that signaling molecules are not static but dynamic entities, changing in numbers and activity over time and space. In the past two decades, researchers have been able to experimentally monitor signaling dynamics and use mathematical techniques to quantify and abstract general principles of how cells process information. In this review, the authors first introduce and discuss various experimental and computational methodologies that have been used to study signaling dynamics. The authors then discuss the different types of temporal dynamics such as oscillations and bistability that can be exhibited by signaling systems and highlight studies that have investigated such dynamics in physiological settings. Finally, the authors illustrate the role of spatial compartmentalization in regulating cellular responses with examples of second-messenger signaling in cardiac myocytes.
可以说，生命和非生命物质最主要的区别之一是感知环境变化并做出适当反应的能力——这种能力存在于每个活细胞中。在单个细胞内，这种功能主要是通过信号分子网络来执行的。然而，信号网络如何帮助细胞做出复杂决策的细节尚不清楚。例如，细胞如何读取渐变的、模拟的压力信号，但将其转化为生死存亡的数字响应？这些问题的答案可能源于这样一个事实，即信号分子不是静态的，而是动态的实体，它们的数量和活性会随时间和空间而变化。在过去的二十年中，研究人员已经能够通过实验监测信号动态，并使用数学技术来量化和抽象细胞处理信息的一般原理。在这篇综述中，作者首先介绍和讨论了用于研究信号动态的各种实验和计算方法。然后，作者讨论了信号系统可以表现出的不同类型的时间动态，如振荡和双稳定性，并强调了在生理环境中研究这些动态的研究。最后，作者通过心肌细胞中二信使信号的例子说明了空间分隔在调节细胞反应中的作用。
