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

非洲锥虫的计算机模型：在复杂环境中移动

• 批准号: 504947458
• 负责人: Professor Dr. Holger Stark
• 金额: --
• 依托单位: Institut für Theoretische Physik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/504947458?language=en
• 关键词: silico; model; African; trypanosome; Moving

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.

布鲁氏锥虫是一种单细胞寄生虫，可引起睡眠疾病，对人类的致命疾病以及牲畜的致命疾病。锥虫的细胞体具有主轴的形状，并附有真核生物鞭毛。沿鞭毛弯曲的弯曲波动时，锥虫表现出特征变形并向前移动。在先前的工作中，我们使用实时细胞分析中的信息与M. Engstler组密切合作，开发了一种准确的锥虫模型锥虫模型。它很好地模仿了真正的锥体的游泳行为，并允许在计算机突变体中学习。虽然非洲锥虫体被认为是在血液中驻留和移动的，但过去十年的研究清楚地表明，大量的研究表明寄生虫也可以在血管外部的组织中发现。锥虫在皮肤，脂肪组织，间质空间和大脑的复杂环境中移动。当进入新环境或需要在脂肪细胞之间游泳时，他们必须在紧密的通道中挤压。在细胞外基质中，它们会遇到形成密集的弹性网络的胶原蛋白纤维，或者与脂肪细胞及其弹性表面的包装相互作用。他们经历了间质流体的流动。该项目的目的是与M. Engstler组的实验密切合作的彻底计算研究，即在复杂环境中如何在包括流体流动的复杂环境中移动，包括我们的流体流动，包括我们使用多粒子碰撞动力学的方法模拟。逐步提高环境的复杂性，我们旨在充分了解不同特征如何影响锥虫的游泳道路。具体而言，我们将研究在限制几何形状的硅锥体中的游泳。为此，我们以越来越多的限制和限制以及障碍物阵列来实施微通道，我们在这里寻找几何游泳。然后，我们允许环境中两种弹性变形。使用珠子弹簧链，我们将建模高度可变形的胶原网络变化的密度和纤维刚度。最后，我们将使用赫兹（Hertzian）接触力实施软障碍物，在脂肪组织中游泳。这使我们更接近真实的环境。