Yildirim Necmettin, Santillan Moises, Horike Daisuke, Mackey Michael C
Centre for Nonlinear Dynamics, McGill University, Montreal, Quebec H3G 1Y6, Canada.
Chaos. 2004 Jun;14(2):279-92. doi: 10.1063/1.1689451.
It is known that the lac operon regulatory pathway is capable of showing bistable behavior. This is an important complex feature, arising from the nonlinearity of the involved mechanisms, which is essential to understand the dynamic behavior of this molecular regulatory system. To find which of the mechanisms involved in the regulation of the lac operon is the origin of bistability, we take a previously published model which accounts for the dynamics of mRNA, lactose, allolactose, permease and beta-galactosidase involvement and simplify it by ignoring permease dynamics (assuming a constant permease concentration). To test the behavior of the reduced model, three existing sets of data on beta-galactosidase levels as a function of time are simulated and we obtain a reasonable agreement between the data and the model predictions. The steady states of the reduced model were numerically and analytically analyzed and it was shown that it may indeed display bistability, depending on the extracellular lactose concentration and growth rate.
众所周知,乳糖操纵子调控途径能够表现出双稳态行为。这是一个重要的复杂特征,源于所涉及机制的非线性,对于理解这个分子调控系统的动态行为至关重要。为了找出乳糖操纵子调控中涉及的哪些机制是双稳态的起源,我们采用一个先前发表的模型,该模型考虑了信使核糖核酸(mRNA)、乳糖、别乳糖、通透酶和β-半乳糖苷酶参与的动力学,并通过忽略通透酶动力学(假设通透酶浓度恒定)对其进行简化。为了测试简化模型的行为,我们模拟了三组现有的关于β-半乳糖苷酶水平随时间变化的数据,并且在数据和模型预测之间获得了合理的一致性。对简化模型的稳态进行了数值和解析分析,结果表明,根据细胞外乳糖浓度和生长速率,它确实可能表现出双稳态。