Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan.
PLoS Comput Biol. 2013;9(6):e1003110. doi: 10.1371/journal.pcbi.1003110. Epub 2013 Jun 27.
Populations of cells often switch states as a group to cope with environmental changes such as nutrient availability and cell density. Although the gene circuits that underlie the switches are well understood at the level of single cells, the ways in which such circuits work in concert among many cells to support group-level switches are not fully explored. Experimental studies of microbial quorum sensing show that group-level changes in cellular states occur in either a graded or an all-or-none fashion. Here, we show through numerical simulations and mathematical analysis that these behaviors generally originate from two distinct forms of bistability. The choice of bistability is uniquely determined by a dimensionless parameter that compares the synthesis and the transport of the inducing molecules. The role of the parameter is universal, such that it not only applies to the autoinducing circuits typically found in bacteria but also to the more complex gene circuits involved in transmembrane receptor signaling. Furthermore, in gene circuits with negative feedback, the same dimensionless parameter determines the coherence of group-level transitions from quiescence to a rhythmic state. The set of biochemical parameters in bacterial quorum-sensing circuits appear to be tuned so that the cells can use either type of transition. The design principle identified here serves as the basis for the analysis and control of cellular collective decision making.
细胞群体通常会集体切换状态，以应对环境变化，如营养物质可用性和细胞密度。尽管单个细胞水平的开关所涉及的基因电路已经得到很好的理解，但这些电路在许多细胞中协同工作以支持群体水平开关的方式尚未得到充分探索。微生物群体感应的实验研究表明，细胞状态的群体水平变化以渐变或全有或全无的方式发生。在这里，我们通过数值模拟和数学分析表明，这些行为通常源于两种不同形式的双稳态。双稳态的选择是由一个无量纲参数唯一决定的，该参数比较了诱导分子的合成和运输。该参数的作用是普遍的，不仅适用于通常在细菌中发现的自动诱导电路，也适用于涉及跨膜受体信号转导的更复杂的基因电路。此外，在具有负反馈的基因电路中，相同的无量纲参数决定了从静止到节奏状态的群体水平转变的相干性。细菌群体感应电路中的一组生化参数似乎被调谐，以使细胞能够使用这两种类型的转变。这里确定的设计原则为细胞集体决策的分析和控制提供了基础。
