Department of Bioengineering, James H. Clark Center, Stanford University, Stanford, CA 94305.
Department of Microbiology and Immunology, James H. Clark Center, Stanford University, Stanford, CA 94305.
Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):E5916-E5925. doi: 10.1073/pnas.1722618115. Epub 2018 Jun 11.
In the unicellular parasite the causative agent of human African sleeping sickness, complex swimming behavior is driven by a flagellum laterally attached to the long and slender cell body. Using microfluidic assays, we demonstrated that can penetrate through an orifice smaller than its maximum diameter. Efficient motility and penetration depend on active flagellar beating. To understand how active beating of the flagellum affects the cell body, we genetically engineered to produce anucleate cytoplasts (zoids and minis) with different flagellar attachment configurations and different swimming behaviors. We used cryo-electron tomography (cryo-ET) to visualize zoids and minis vitrified in different motility states. We showed that flagellar wave patterns reflective of their motility states are coupled to cytoskeleton deformation. Based on these observations, we propose a mechanism for how flagellum beating can deform the cell body via a flexible connection between the flagellar axoneme and the cell body. This mechanism may be critical for to disseminate in its host through size-limiting barriers.
在单细胞寄生虫 中,这种导致人类昏睡病的病原体,通过侧向附着在长而细的细胞体上的鞭毛来驱动复杂的游动行为。利用微流控分析,我们证明了 可以穿透比其最大直径小的孔。有效的运动和穿透依赖于活跃的鞭毛拍打。为了了解鞭毛的活跃拍打如何影响细胞体,我们通过基因工程使 产生具有不同鞭毛附着结构和不同游动行为的无核细胞质体(原生质体和微体)。我们使用冷冻电子断层扫描(cryo-ET)来可视化在不同运动状态下冷冻的原生质体和微体。我们表明,反映其运动状态的鞭毛波模式与细胞骨架变形相关联。基于这些观察结果,我们提出了一种机制,即鞭毛的拍打如何通过鞭毛轴丝和细胞体之间的柔性连接来使细胞体变形。这种机制对于 可能通过大小限制屏障在其宿主中传播至关重要。