Ma Wenchuan, Verma Lakshmanji, Lee Huan-Jui, Pan Weichun, Sherman Michael B, Sullivan David J, Rimer Jeffrey D, Palmer Jeremy C, Vekilov Peter G
William A. Brookshire Department of Chemical & Biomolecular Engineering, University of Houston, Houston, TX, USA.
Welch Center for Advanced Bioactive Materials Crystallization, University of Houston, Houston, TX, USA.
Commun Chem. 2025 Aug 13;8(1):246. doi: 10.1038/s42004-025-01612-0.
Organic biocrystals support essential functions or drive pathologies in numerous living organisms. Here we focus on the nucleation of hematin crystals, which form in malaria parasites as a part of their heme detoxification pathway. Suppression of hematin crystal nucleation has proven the most productive strategy to treat malaria, yet little is known about the relevant molecular mechanisms. We show that crystal nucleation can be suppressed and fine-tuned via the properties of a population of precursors that host nonclassical hematin crystal nucleation. The addition of modifiers selectively invokes one of three outcomes: suppressed nucleation, faster nucleation, or no effect. We demonstrate that β-hematin crystal nuclei form within mesoscopic hematin-rich clusters and that the impacts of the modifiers on crystal nucleation parallel their activity towards the nucleation precursors. Molecular simulations reveal that modifiers' activities derive from their interactions with the hematin monomers, dimers, and larger agglomerates. Collectively, these observations support a general method to control crystal nucleation that relies on solute-modifier interactions and their consequences for the nucleation precursors. The proposed rationale offers a powerful tool to control nucleation in areas that employ tailored crystalline materials and helps to understand how crystal assemblies with elaborate superstructures appear in nature.
有机生物晶体在众多生物体中支持基本功能或引发病变。在此，我们聚焦于血晶素晶体的成核过程，血晶素晶体在疟原虫中形成，是其血红素解毒途径的一部分。抑制血晶素晶体成核已被证明是治疗疟疾最有效的策略，但相关分子机制却知之甚少。我们发现，晶体成核可以通过一群承载非经典血晶素晶体成核的前体的性质来抑制和微调。添加改性剂会选择性地引发三种结果之一：抑制成核、加速成核或无影响。我们证明，β - 血晶素晶核在富含血晶素的介观簇中形成，并且改性剂对晶体成核的影响与其对成核前体的活性平行。分子模拟表明，改性剂的活性源于它们与血晶素单体、二聚体及更大聚集体的相互作用。总体而言，这些观察结果支持了一种基于溶质 - 改性剂相互作用及其对成核前体影响的控制晶体成核的通用方法。所提出的原理为在使用定制晶体材料的领域控制成核提供了有力工具，并有助于理解自然界中具有精细超结构的晶体聚集体是如何出现的。
