Alizadehrad Davod, Krüger Timothy, Engstler Markus, Stark Holger
Institute of Theoretical Physics, Technische Universität Berlin, Berlin, Germany.
Department of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, Germany.
PLoS Comput Biol. 2015 Jan 8;11(1):e1003967. doi: 10.1371/journal.pcbi.1003967. eCollection 2015 Jan.
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.
鞭毛虫布氏锥虫在感染哺乳动物宿主时会引发昏睡病，其经历一个复杂的生命周期。它具有相当复杂的推进机制，并在多种微环境中游动。这些微环境不断施加选择压力，锥虫通过其结构和行为来适应。因此，锥虫在其生命周期中呈现出多种复杂的形态类型。然而，尽管细胞生物学已详细研究了其中大多数的形态和功能，但关于大多数形态类型的动态行为和发育的实验数据仍然缺乏。在此，我们表明模拟科学可以通过对一个精确的、受自然启发的细胞模型进行特定且可控的修改来预测中间细胞设计，该模型是我们利用活细胞分析的信息开发的。这些细胞模型考虑了真实锥虫形态类型的几个重要特征，例如细胞体的几何形状和弹性特性，以及它们使用真核鞭毛的游动机制。我们为细胞体引入一个弹性网络模型，包括弯曲刚度，并使用称为多粒子碰撞动力学的中尺度模拟技术在流体环境中模拟游动。血液期的计算机模拟锥虫呈现出体内特征性的旋转和平移运动模式，这对于在脊椎动物宿主中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路径是在粘性流体中产生观察到的游动行为的一个重要方面，也是达到最大游动速度所必需的。改变鞭毛附着的细节会产生效率较低的游动者。我们还模拟了寄生虫在采采蝇体内发育过程中出现的不同形态类型，并预测了一条我们目前在实验中尚未能够测量的鞭毛路径。
