Effect of malaria parasite shape on its alignment at erythrocyte membrane.

Effect of malaria parasite shape on its alignment at erythrocyte membrane.
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DOI:
10.7554/elife.68818
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发表时间:
2021-07-21
期刊:
影响因子:
7.7
通讯作者:
Fedosov DA
Fedosov DA
中科院分区:
生物学1区
文献类型:
--
作者:
Dasanna AK;Hillringhaus S;Gompper G;Fedosov DA

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在疟疾发病的血液阶段,寄生虫侵入健康的红细胞(RBC),在宿主体内繁殖,逃避免疫反应。当附着在红细胞上时,寄生虫首先必须将其顶点与膜对齐以成功入侵。由于寄生虫的顶点位于具有大的局部曲率的椭圆形(蛋形)的尖端,因此顶点对齐通常是能量上不利的过程。先前,使用粗粒度介观模拟,我们已经表明,由于RBC膜变形和寄生虫与RBC膜之间基于键的相互作用的随机性质,实现了最佳对准时间(Hillringhaus等人,2020年)。在这里,我们证明了寄生虫的形状有一个突出的对齐过程中的影响。球形寄生虫的对齐时间为中间和大键的解离率(或弱膜寄生虫相互作用)被发现是接近那些的鸡蛋形状。然而,对于小的键解离速率(或强粘附和大的膜变形),球形形状的对准时间急剧增加。寄生虫的形状与大的纵横比,如扁圆和长扁长椭球体被发现表现出很长的对齐时间相比,鸡蛋状的形状。在一个僵硬的红细胞,球形寄生虫对齐速度比任何其他研究的形状。这项研究表明,原始的鸡蛋状形状的寄生虫对齐性能不差于其他考虑的形状,但更强大的不同的粘附相互作用和红细胞膜刚度。
During the blood stage of malaria pathogenesis, parasites invade healthy red blood cells (RBC) to multiply inside the host and evade the immune response. When attached to RBC, the parasite first has to align its apex with the membrane for a successful invasion. Since the parasite’s apex sits at the pointed end of an oval (egg-like) shape with a large local curvature, apical alignment is in general an energetically unfavorable process. Previously, using coarse-grained mesoscopic simulations, we have shown that optimal alignment time is achieved due to RBC membrane deformation and the stochastic nature of bond-based interactions between the parasite and RBC membrane (Hillringhaus et al., 2020). Here, we demonstrate that the parasite’s shape has a prominent effect on the alignment process. The alignment times of spherical parasites for intermediate and large bond off-rates (or weak membrane-parasite interactions) are found to be close to those of an egg-like shape. However, for small bond off-rates (or strong adhesion and large membrane deformations), the alignment time for a spherical shape increases drastically. Parasite shapes with large aspect ratios such as oblate and long prolate ellipsoids are found to exhibit very long alignment times in comparison to the egg-like shape. At a stiffened RBC, a spherical parasite aligns faster than any other investigated shape. This study shows that the original egg-like shape performs not worse for parasite alignment than other considered shapes but is more robust with respect to different adhesion interactions and RBC membrane rigidities.