大肠杆菌鞭毛马达对信号分子浓度响应的力学特性

Bacteria are closely related to humans. Bacteria are used by humans for many purposes, such as industrial and food productions, and some of them are responsible for human health and diseases. Some species, such as E.coli, are able to swim in aqueous environment by rotating peritrichous flagella, each is driven by a reversible rotatory molecular machine at its base, which is flagellar motor. And their motility result from rotation of flagellar motor play important role in pathogenicity. The flagellar motor is self-assembled from a variety of proteins, which can adapt to different environments by changing the quantity or the type of component proteins. As the power output unit, flagellar motor can respond to external load directly. The signal protein CheY controls of motor switch after phosphorylated, and flagellar motor is ultrasensitive to the signal molecule concentration in the cell, researches have shown this property can be affected by load, but lack of direct data to illustrate. In this project, we will measure the response curve of flagellar motor of E.coli versus the signal concentration, and clarify the internal mechanism. Studies of this mechanics characteristic will promotes the understanding of bacteria motility and its mechanical regulation mechanism, helps develop new antibacterial means in the future, and even provides a theoretical basis for the manufacture of self-assembled molecular motors.

细菌与人类的关系十分密切，自然界中一些种类的细菌，如大肠杆菌，其致病性与其运动有十分紧密的联系，这些细菌通过胞体上生长的螺旋形鞭毛驱动自身的游动，每根鞭毛由一个可反转的分子机器驱动，这一分子机器就是鞭毛马达。鞭毛马达由多种蛋白自组装而成，本身会对不同的环境做出相应的变化，可以改变自身组分蛋白的数量甚至类型。鞭毛马达作为细菌运动的动力输出单元，对外界负载的变化有直接的响应。磷酸化的CheY分子控制马达的转向，马达对其浓度的响应十分灵敏，研究表明负载会对这一特性产生一定的影响，但负载对其产生的影响缺乏直接的数据支持。本项目将以多个实验测量不同负载下大肠杆菌鞭毛马达对信号分子浓度的响应曲线，并阐明其内部机制。对鞭毛马达的这一力学特性的研究有助于对细菌运动行为及其力学调控机制的进一步认识，帮助未来发展新的抗菌手段，甚至为制造自组装分子马达提供一定的理论依据。

细菌鞭毛马达是自然界中存在的一种精密的蛋白质分子机器，作为细菌的动力单元，对于其力学特性的研究一直是研究热点。鞭毛马达的转向同时受到内部信号分子的控制，细菌根据外界刺激，调节胞内信号分子的浓度从而控制马达的转向，进而控制自身的游动行为。本项目执行过程中，我们发现了集群运动中细菌倒退行为产生的新机制，即使没有信号分子的参与，细菌在集群中仍然可以实现倒退行为。通过对细菌的三维追踪，我们测量了细菌的扩散行为，发现野生型细菌采取Lévy walk的随机运动模式探索环境，这一模式的产生来源于细菌内部信号分子浓度的波动。我们也详细测量了不同负载下鞭毛马达的剂量响应曲线，填补了数据空白。项目执行期间发表SCI论文2篇，Frontiers in Microbiology和 Applied and Environmental Microbiology各一篇。另有一篇文章正在筹备中。