An in silico model of the African trypanosome: Moving in complex environments

布鲁氏锥虫是一种单细胞寄生虫，它会导致昏睡病，这是一种对人类和牲畜都致命的疾病。锥虫的细胞体呈纺锤形，其上附着有真核鞭毛。当弯曲波沿着鞭毛移动时，锥虫会表现出特有的变形并向前移动。在以前的工作中，我们已经利用活细胞分析的信息，与M.Engstler的团队密切合作，开发了一个准确的电子计算机模型锥虫。它很好地模拟了真正锥虫的游泳行为，并允许在硅变种动物中进行研究。虽然非洲布氏锥虫一直被认为居住在血液中并在血液中移动，但过去十年的研究清楚地表明，在血管外的组织中也可以发现大量的这种寄生虫。锥虫在皮肤、脂肪组织、间质和大脑的复杂环境中运动。当进入一个新的环境或需要在脂肪细胞之间游泳时，它们必须挤过狭窄的通道。在细胞外基质中，它们遇到形成密集弹性网络的胶原纤维，或者它们与脂肪细胞及其弹性表面的堆积相互作用。他们体验间隙流体的流动。该项目的目标是与M.Engstler小组的实验密切合作，深入计算研究硅锥虫如何在包括流体流动在内的复杂环境中运动，这是我们用多粒子碰撞动力学方法模拟的。逐步增加环境的复杂性，我们的目标是充分了解不同的特征如何影响锥虫的游泳路径。具体地说，我们将研究硅锥虫在限制几何中也在流动中的游泳。为此，我们实现了增加限制和收缩的微通道，以及障碍阵列，其中我们寻找几何游泳。然后，我们考虑环境中的两种类型的弹性变形。使用珠弹簧链，我们将模拟不同密度和纤维硬度的高度变形的胶原蛋白网络。最后，我们将通过使用赫兹接触力实现软障碍来处理脂肪组织中的游泳。这让我们更接近真实的环境。

Trypanosoma brucei is a uni-cellular parasite that causes the sleeping sickness, a deadly disease for humans and also for livestock. The cell body of the trypanosome has the shape of a spindle, along which an eukaryotic flagellum is attached. While a bending wave runs along the flagellum, the trypanosome exhibits characteristic deformations and moves forward. In previous work we have developed an accurate, in silico model trypanosome in close collaboration with the group of M. Engstler using information from live cell analyses. It mimics the swimming behavior of the real trypanosome very well and allows to study in silico mutants.While the African trypanosome brucei has been considered to reside and move in the blood stream, research of the last decade has clearly shown that a substantial amount of the parasite can also be found in tissues outside the blood vessels. Trypanosomes move in the complex environment of the skin, fat tissue, in the interstitial space, and the brain. They have to squeeze through tight passages when entering a new environment or need to swim between fat cells. In the extracellular matrix they encounter collagen fibers forming a dense elastic network or they interact with a packing of fat cells and their elastic surfaces. And they experience the flow of the interstitial fluid.The goal of the project is a thorough computational investigation, in close cooperation with experiments in the group of M. Engstler, of how the in silico trypanosome moves in complex environments including fluid flow, which we simulate with the method of multi-particle collision dynamics. Increasing the complexity of the environment step by step, we aim for a full understanding how different features influence the swimming path of the trypanosome. Concretely, we will investigate the swimming in silico trypanosome in confining geometries also in flow. For this, we implement microchannels with increasing confinement as well as constrictions, and also obstacle arrays, where we look for geometric swimming. We then allow for two types of elastic deformations in the environment. Using bead-spring chains, we will model the highly deformable collagen network varying density and fiber stiffness. Finally, we will approach swimming in fat tissue by implementing soft obstacles using Hertzian contact forces. This brings us closer to real environments.