Center for Theoretical Biology and School of Physics, Peking University, Beijing, China.
PLoS Comput Biol. 2010 Apr 8;6(4):e1000735. doi: 10.1371/journal.pcbi.1000735.
Escherichia coli chemotactic motion in spatiotemporally varying environments is studied by using a computational model based on a coarse-grained description of the intracellular signaling pathway dynamics. We find that the cell's chemotaxis drift velocity v(d) is a constant in an exponential attractant concentration gradient [L] proportional, variantexp(Gx). v(d) depends linearly on the exponential gradient G before it saturates when G is larger than a critical value G(C). We find that G(C) is determined by the intracellular adaptation rate k(R) with a simple scaling law: G(C) infinity k(1/2)(R). The linear dependence of v(d) on G = d(ln[L])/dx directly demonstrates E. coli's ability in sensing the derivative of the logarithmic attractant concentration. The existence of the limiting gradient G(C) and its scaling with k(R) are explained by the underlying intracellular adaptation dynamics and the flagellar motor response characteristics. For individual cells, we find that the overall average run length in an exponential gradient is longer than that in a homogeneous environment, which is caused by the constant kinase activity shift (decrease). The forward runs (up the gradient) are longer than the backward runs, as expected; and depending on the exact gradient, the (shorter) backward runs can be comparable to runs in a spatially homogeneous environment, consistent with previous experiments. In (spatial) ligand gradients that also vary in time, the chemotaxis motion is damped as the frequency omega of the time-varying spatial gradient becomes faster than a critical value omega(c), which is controlled by the cell's chemotaxis adaptation rate k(R). Finally, our model, with no adjustable parameters, agrees quantitatively with the classical capillary assay experiments where the attractant concentration changes both in space and time. Our model can thus be used to study E. coli chemotaxis behavior in arbitrary spatiotemporally varying environments. Further experiments are suggested to test some of the model predictions.
我们基于细胞内信号转导通路动力学的粗粒化描述,利用计算模型研究了时空变化环境中大肠杆菌的趋化运动。我们发现,细胞的趋化漂移速度 v(d) 在与指数趋化剂浓度梯度[L]成正比的比例项 variantexp(Gx) 中是一个常数。在 G 大于临界值 G(C) 之前,v(d) 与指数梯度 G 呈线性关系,当 G 大于 G(C) 时,v(d) 会饱和。我们发现,G(C) 由细胞内适应率 k(R) 决定,具有简单的标度律:G(C) infinity k(1/2)(R)。v(d) 与 G = d(ln[L])/dx 的线性关系直接证明了大肠杆菌感知对数趋化剂浓度导数的能力。限制梯度 G(C) 的存在及其与 k(R) 的标度关系,可由细胞内适应动力学和鞭毛马达响应特性来解释。对于单个细胞,我们发现,在指数梯度中,整体平均奔跑长度比在均匀环境中长,这是由于激酶活性的恒定变化(降低)引起的。与预期的一样,前向奔跑(沿梯度向上)比后向奔跑长;并且取决于具体的梯度,较短的后向奔跑可以与在空间均匀环境中的奔跑相当,这与之前的实验结果一致。在随时间变化的(空间)配体梯度中,当时间变化的空间梯度的频率 omega 变得快于临界值 omega(c) 时,趋化运动就会被阻尼,omega(c) 由细胞的趋化适应率 k(R) 控制。最后,我们的模型没有可调参数,与经典的毛细管测定实验定量吻合,其中趋化剂浓度在空间和时间上都发生了变化。因此,我们的模型可以用于研究任意时空变化环境中大肠杆菌的趋化行为。建议进行进一步的实验以测试模型的一些预测。