Temperature-Induced Catch-Slip to Slip Bond Transit in Plasmodium falciparum-Infected Erythrocytes
Temperature-Induced Catch-Slip to Slip Bond Transit in Plasmodium falciparum-Infected Erythrocytes
复制标题
恶性疟原虫感染的红细胞中温度诱导的捕捉滑移到滑移键转变
DOI：
10.1016/j.bpj.2019.11.016
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发表时间：
2020
影响因子：
3.4
通讯作者：
Lim, C. T.
中科院分区：
文献类型：
--
作者：
Lim, Y. B.;Thingna, J.;Kong, F.;Dao, M.;Cao, J.;Lim, C. T.
恶性疟原虫感染的红细胞（IRBC）或红细胞通过粘附于宿主内皮细胞来避免脾清除。内皮受体细胞间粘附分子-1（ICAM-1）和分化簇36（CD 36）的上调与严重疾病病理学相关。大多数IRBC与这些分子相互作用的体外研究是在室温下进行的。然而，由于IRBC暴露于宿主中37°C（体温）和41°C（发热温度）之间的温度变化，因此了解这些生理相关温度下的IRBC-受体相互作用非常重要。在这里，我们在37和41°C下探测IRBC与ICAM-1和CD 36的相互作用。单键力钳光谱用于确定键的解离速率，因此，解开IRBC-受体相互作用的性质。关联率也提取从一个多键流测定使用细胞随机模型。令人惊讶的是，IRBC-ICAM-1键从37°C下的捕捉-滑动键向41°C下的滑动键转变。此外，IRBC-ICAM-1和IRBC-CD 36的结合亲和力随着温度从37 ° C升高至41°C而降低。这项研究强调了在生理相关温度下检测受体-配体相互作用的重要性，并揭示了恶性疟原虫细胞粘附键的温度依赖性的生物物理学见解。
Plasmodium falciparummalaria-infected red blood cells (IRBCs), or erythrocytes, avoid splenic clearance by adhering to host endothelium. Upregulation of endothelial receptors intercellular adhesion molecule-1 (ICAM-1) and cluster of differentiation 36 (CD36) are associated with severe disease pathology. Most in vitro studies of IRBCs interacting with these molecules were conducted at room temperature. However, as IRBCs are exposed to temperature variations between 37°C (body temperature) and 41°C (febrile temperature) in the host, it is important to understand IRBC-receptor interactions at these physiologically relevant temperatures. Here, we probe IRBC interactions against ICAM-1 and CD36 at 37 and 41°C. Single bond force-clamp spectroscopy is used to determine the bond dissociation rates and hence, unravel the nature of the IRBC-receptor interaction. The association rates are also extracted from a multiple bond flow assay using a cellular stochastic model. Surprisingly, IRBC-ICAM-1 bond transits from a catch-slip bond at 37°C toward a slip bond at 41°C. Moreover, binding affinities of both IRBC-ICAM-1 and IRBC-CD36 decrease as the temperature rises from 37 to 41°C. This study highlights the significance of examining receptor-ligand interactions at physiologically relevant temperatures and reveals biophysical insight into the temperature dependence ofP. falciparummalaria cytoadherent bonds.