Antagonistic cooperativity between crystal growth modifiers
Antagonistic cooperativity between crystal growth modifiers
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DOI：
10.1038/s41586-019-1918-4
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发表时间：
2020-01-01
期刊：
影响因子：
64.8
通讯作者：
Vekilov, Peter G.
中科院分区：
文献类型：
--
作者：
Ma, Wenchuan;Lutsko, James F.;Vekilov, Peter G.
抑制血色素结晶的抑制剂对是疟原虫生理学的一部分，由于扭结阻断剂减弱了阶梯钉扎，因此显示出意想不到的拮抗作用。在自然界和工业中普遍存在的过程利用了多组分环境中的结晶（1-5）;然而，实验室的努力集中在纯溶质的结晶（6，7）和单一生长调节剂的影响（8，9）。在这里，我们研究了抑制剂对阻断血红素结晶的分子机制，血红素是一种与疟疾寄生虫生理学相关的模型有机化合物（10，11）。我们使用扫描探针显微镜和分子建模的组合来证明抑制剂对，其成分采用不同的血红素生长抑制、扭结阻断和阶梯钉扎机制（12，13），根据抑制剂组合和应用浓度表现出协同和拮抗协同性。两种晶体生长调节剂之间的协同作用是预期的，但血红素抑制剂的拮抗协同作用没有反映在目前的晶体生长模型。我们证明，扭结阻滞剂减少了线张力的步骤边缘，这有利于晶体层的成核和步骤通过步骤pinners创建的栅极传播。结晶改性剂之间的协同作用的分子观点提供指导的结晶材料的合成中的改性剂的配对。所提出的机制指出了理解和控制自然和工程系统中结晶的策略，这发生在复杂的多组分介质中（1- 3，8，9）。在更广泛的背景下，我们的研究结果突出了晶体界面的结构和动力学介导的晶体-改性剂相互作用的复杂性。
Inhibitor pairs that suppress the crystallization of haematin, which is a part of malaria parasites' physiology, show unexpected antagonism due to attenuation of step pinning by kink blockers.Ubiquitous processes in nature and the industry exploit crystallization from multicomponent environments(1-5); however, laboratory efforts have focused on the crystallization of pure solutes(6,7) and the effects of single growth modifiers(8,9). Here we examine the molecular mechanisms employed by pairs of inhibitors in blocking the crystallization of haematin, which is a model organic compound with relevance to the physiology of malaria parasites(10,11). We use a combination of scanning probe microscopy and molecular modelling to demonstrate that inhibitor pairs, whose constituents adopt distinct mechanisms of haematin growth inhibition, kink blocking and step pinning(12,13), exhibit both synergistic and antagonistic cooperativity depending on the inhibitor combination and applied concentrations. Synergism between two crystal growth modifiers is expected, but the antagonistic cooperativity of haematin inhibitors is not reflected in current crystal growth models. We demonstrate that kink blockers reduce the line tension of step edges, which facilitates both the nucleation of crystal layers and step propagation through the gates created by step pinners. The molecular viewpoint on cooperativity between crystallization modifiers provides guidance on the pairing of modifiers in the synthesis of crystalline materials. The proposed mechanisms indicate strategies to understand and control crystallization in both natural and engineered systems, which occurs in complex multicomponent media(1-3,8,9). In a broader context, our results highlight the complexity of crystal-modifier interactions mediated by the structure and dynamics of the crystal interface.