Structural determinants and function of chirality in the motion of malaria parasites

手性存在于从分子到细胞到生物体水平的生物系统中，但很难将其跨尺度联系起来。在这里，我们建议对疟原虫家族的成员做到这一点，疟原虫家族是疟疾的病原体。它的三种运动形式中的两种，子孢子和动合子，已知在三维环境中以螺旋轨道运动。弓形虫速殖子形式也是如此，它是顶复门的一个密切相关的成员，也是弓形虫病的病原体。有几个潜在的候选人的寄生虫手性的分子机制，包括在微管紧身衣，在顶端环复合物或肌动球蛋白介导的表面流的手性元素。此外，细胞运动中的手性可能取决于这些结构元素与环境的相互作用，包括其几何和机械特性。螺旋运动的进化益处可能在于在弹性环境中有效的力传递，而且还在于找到目标结构或细胞的效率。我们将结合联合收割机先进的成像，牵引力显微镜和有针对性的突变与数学模型的自推进手性颗粒和疟原虫子孢子的微机械模型，以确定占主导地位的分子效应，并阐明其成功感染的进化优势。

Chirality is present in biological systems from the molecular through the cellular to the organismal level, but it is difficult to connect it across scales. Here we suggest to accomplish this for the members of the Plasmodium family, which are the causative agents of malaria. Two of its three motile forms, the sporozoites and the ookinetes, are known to move on helical trajectories in three-dimensional environments. The same holds true for the tachyzoite form of Toxoplasma gondii, a closely related member of the phylum apicomplexa and the causative agent of toxoplasmosis. There are several potential candidates for the molecular mechanisms underlying parasite chirality, including chiral elements in the microtubule corset, in the apical ring complex or in the actomyosin-mediated surface flow. Moreover, chirality in the cell movement might be determined by the interplay of such structural elements with the environment, including its geometrical and mechanical properties. The evolutionary benefits of helical motion might lie in efficient force transmission in elastic environments, but also in the efficiency of finding target structures or cells. We will combine advanced imaging, traction force microscopy and targeted mutations with mathematical models for self-propelled chiral particles and micromechanical models for Plasmodium sporozoites to identify the dominating molecular effect and to shed light on its evolutionary advantage for successful infections.