Simulating the Complex Cell Design of Trypanosoma brucei and Its Motility
Simulating the Complex Cell Design of Trypanosoma brucei and Its Motility
复制标题
DOI：
10.1371/journal.pcbi.1003967
复制
发表时间：
2015-01-01
影响因子：
4.3
通讯作者：
Stark, Holger
中科院分区：
文献类型：
--
作者：
Alizadehrad, Davod;Krueger, Timothy;Stark, Holger
布氏锥虫是一种鞭毛虫，在感染哺乳动物宿主时会引起昏睡病，它经历了一个复杂的生活史。它有一个相当复杂的推进机制，在不同的微环境中游泳。这些持续施加选择性压力，锥虫根据其结构和行为进行调整。因此，锥虫在其生命周期中呈现出各种复杂的形态类型。然而，虽然细胞生物学中的大多数形态和功能都有详细的形式和功能，但关于大多数形态类型的动态行为和发育的实验数据还很缺乏。在这里，我们展示了模拟科学可以通过对精确的、受自然启发的细胞模型进行特定和受控的修改来预测中间细胞设计，该模型是我们利用来自活细胞分析的信息开发的。这些细胞模型解释了真实锥体形态的几个重要特征，如细胞体的几何和弹性性质，以及它们使用真核鞭毛的游泳机制。我们引入了一种弹性网络模型来描述细胞体，包括弯曲刚度和模拟流体环境中的游泳，使用了被称为多粒子碰撞动力学的中尺度模拟技术。血液中的硅锥体表现出体内特有的旋转和平移运动模式，这对脊椎动物宿主的生存和毒力至关重要。此外，我们的模型准确地模拟了锥虫的翻滚和向后运动。我们表明，附着在细胞体周围的鞭毛的独特轨迹是在粘性流体中产生所观察到的游泳行为的一个重要方面，也是达到最大游泳速度所必需的。改变鞭毛附着的细节会降低游泳者的效率。我们还模拟了采采蝇体内寄生虫发育过程中出现的不同形态，并预测了到目前为止我们还无法在实验中测量到的鞭毛路线。
The flagellate Trypanosoma brucei, which causes the sleeping sickness when infecting a mammalian host, goes through an intricate life cycle. It has a rather complex propulsion mechanism and swims in diverse microenvironments. These continuously exert selective pressure, to which the trypanosome adjusts with its architecture and behavior. As a result, the trypanosome assumes a diversity of complex morphotypes during its life cycle. However, although cell biology has detailed form and function of most of them, experimental data on the dynamic behavior and development of most morphotypes is lacking. Here we show that simulation science can predict intermediate cell designs by conducting specific and controlled modifications of an accurate, nature-inspired cell model, which we developed using information from live cell analyses. The cell models account for several important characteristics of the real trypanosomal morphotypes, such as the geometry and elastic properties of the cell body, and their swimming mechanism using an eukaryotic flagellum. We introduce an elastic network model for the cell body, including bending rigidity and simulate swimming in a fluid environment, using the mesoscale simulation technique called multi-particle collision dynamics. The in silico trypanosome of the bloodstream form displays the characteristic in vivo rotational and translational motility pattern that is crucial for survival and virulence in the vertebrate host. Moreover, our model accurately simulates the trypanosome's tumbling and backward motion. We show that the distinctive course of the attached flagellum around the cell body is one important aspect to produce the observed swimming behavior in a viscous fluid, and also required to reach the maximal swimming velocity. Changing details of the flagellar attachment generates less efficient swimmers. We also simulate different morphotypes that occur during the parasite's development in the tsetse fly, and predict a flagellar course we have not been able to measure in experiments so far.