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.

布氏锥虫是一种单细胞寄生虫，会引起昏睡病，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，真核鞭毛沿着附着。当弯曲波沿着鞭毛运动时，锥虫表现出特征性的变形并向前运动。在以前的工作中，我们与M. Engstler使用来自活细胞分析的信息。它很好地模拟了真实的锥虫的游动行为，并允许在计算机上研究突变体。虽然非洲布氏锥虫一直被认为在血液中居住和移动，但过去十年的研究清楚地表明，大量的寄生虫也可以在血管外的组织中发现。锥虫在皮肤、脂肪组织、间隙空间和大脑的复杂环境中移动。它们在进入新环境时必须通过狭窄的通道，或者需要在脂肪细胞之间游动。在细胞外基质中，它们遇到形成致密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。该项目的目标是通过与M。Engstler，计算机锥虫如何在包括流体流动的复杂环境中移动，我们用多粒子碰撞动力学方法模拟。逐步增加环境的复杂性，我们的目标是充分了解不同的功能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形状也在流动中的游泳。为此，我们实施微通道越来越多的限制以及收缩，也障碍阵列，在那里我们寻找几何游泳。然后，我们允许在环境中的两种类型的弹性变形。使用珠弹簧链，我们将模拟高度可变形的胶原蛋白网络变化的密度和纤维刚度。最后，我们将通过使用赫兹接触力实现软障碍来接近在脂肪组织中游泳。这使我们更接近真实的环境。