Division of Molecular Biosciences, Imperial College London, London, United Kingdom.
Biophys J. 2013 Apr 16;104(8):1824-31. doi: 10.1016/j.bpj.2013.02.028.
Many biological, physical, and social interactions have a particular dependence on where they take place; e.g., in living cells, protein movement between the nucleus and cytoplasm affects cellular responses (i.e., proteins must be present in the nucleus to regulate their target genes). Here we use recent developments from dynamical systems and chemical reaction network theory to identify and characterize the key-role of the spatial organization of eukaryotic cells in cellular information processing. In particular, the existence of distinct compartments plays a pivotal role in whether a system is capable of multistationarity (multiple response states), and is thus directly linked to the amount of information that the signaling molecules can represent in the nucleus. Multistationarity provides a mechanism for switching between different response states in cell signaling systems and enables multiple outcomes for cellular-decision making. We combine different mathematical techniques to provide a heuristic procedure to determine if a system has the capacity for multiple steady states, and find conditions that ensure that multiple steady states cannot occur. Notably, we find that introducing species localization can alter the capacity for multistationarity, and we mathematically demonstrate that shuttling confers flexibility for and greater control of the emergence of an all-or-nothing response of a cell.
许多生物、物理和社会相互作用特别依赖于它们发生的地点;例如,在活细胞中,蛋白质在核和细胞质之间的运动影响细胞反应(即,蛋白质必须存在于核中以调节其靶基因)。在这里,我们使用动力系统和化学反应网络理论的最新进展来识别和描述真核细胞的空间组织在细胞信息处理中的关键作用。特别是,不同隔室的存在在系统是否能够具有多稳定性(多个响应状态)方面起着关键作用,因此与信号分子在核中能够表示的信息量直接相关。多稳定性为细胞信号系统中的不同响应状态之间的切换提供了一种机制,并为细胞决策提供了多种结果。我们结合了不同的数学技术,提供了一种启发式程序来确定系统是否具有多个稳定状态的能力,并找到了确保多个稳定状态不会发生的条件。值得注意的是,我们发现引入物种定位可以改变多稳定性的能力,并且我们从数学上证明了穿梭赋予了细胞全有或全无反应出现的灵活性和更大的控制。