Kalinin Yevgeniy V, Jiang Lili, Tu Yuhai, Wu Mingming
School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14853, USA.
Biophys J. 2009 Mar 18;96(6):2439-48. doi: 10.1016/j.bpj.2008.10.027.
We studied the response of swimming Escherichia coli (E. coli) bacteria in a comprehensive set of well-controlled chemical concentration gradients using a newly developed microfluidic device and cell tracking imaging technique. In parallel, we carried out a multi-scale theoretical modeling of bacterial chemotaxis taking into account the relevant internal signaling pathway dynamics, and predicted bacterial chemotactic responses at the cellular level. By measuring the E. coli cell density profiles across the microfluidic channel at various spatial gradients of ligand concentration grad[L] and the average ligand concentration [L] near the peak chemotactic response region, we demonstrated unambiguously in both experiments and model simulation that the mean chemotactic drift velocity of E. coli cells increased monotonically with grad [L]/[L] or approximately grad(log[L])--that is E. coli cells sense the spatial gradient of the logarithmic ligand concentration. The exact range of the log-sensing regime was determined. The agreements between the experiments and the multi-scale model simulation verify the validity of the theoretical model, and revealed that the key microscopic mechanism for logarithmic sensing in bacterial chemotaxis is the adaptation kinetics, in contrast to explanations based directly on ligand occupancy.
我们使用新开发的微流控装置和细胞追踪成像技术,在一系列严格控制的化学浓度梯度条件下,研究了游泳状态的大肠杆菌的反应。同时,我们进行了细菌趋化性的多尺度理论建模,考虑了相关的内部信号通路动力学,并预测了细胞水平上的细菌趋化反应。通过测量在配体浓度梯度grad[L]的各种空间梯度以及趋化反应峰值区域附近的平均配体浓度[L]条件下,微流控通道中大肠杆菌的细胞密度分布,我们在实验和模型模拟中都明确证明,大肠杆菌细胞的平均趋化漂移速度随grad[L]/[L]或近似随grad(log[L])单调增加,即大肠杆菌细胞能够感知对数配体浓度的空间梯度。确定了对数感知机制的精确范围。实验与多尺度模型模拟之间的一致性验证了理论模型的有效性,并揭示了细菌趋化性中对数感知的关键微观机制是适应动力学,这与直接基于配体占据情况的解释形成对比。