胆固醇结晶测试了分子生长和溶解途径的微观可逆性极限

摘要(中文译文)

在结晶学领域，一个常被讨论的问题是：在远离平衡态的条件下，生长与溶解这两个相反的过程是否遵循微观可逆性。这对于非经典生长路径尤为相关，例如颗粒附着结晶（CPA），该过程由于涉及前驱体附着于晶体表面、随后在其整合入底层晶体的过程中发生无序到有序转变这一独特步骤序列，因而是一个不可逆过程。晶体溶解的逆过程通常与未完成层的回缩相关，这与经典生长相反，且与CPA明显不同。在此，我们选择胆固醇作为模型体系，基于其在生理环境中的普遍存在，且能够在过饱和（晶体生长）与欠饱和（晶体溶解）条件之间切换。我们利用近期观察到的结果，即胆固醇的成核与生长分别通过非经典和经典路径发生。我们的发现揭示了在中等欠饱和溶液中微观可逆性的局限，此时溶解通过一种独特的非经典路径发生，涉及在晶体表面形成富胆固醇簇。在簇形成后尝试再生晶体表面生长表明，它们对结晶具有不可逆的影响，其方式可能抑制病理性胆固醇沉淀。

Abstract

A subject often debated in the field of crystallization is whether opposing processes of growth and dissolution abide by microscopic reversibility under conditions far from equilibrium. This is particularly relevant for nonclassical growth pathways such as crystallization by particle attachment (CPA), which is an irreversible process owing to the unique sequence of steps involving precursor attachment to crystal surfaces followed by their disorder-to-order transitions as they integrate into the underlying crystal. The reverse process of crystal dissolution is frequently associated with the retraction of unfinished layers, which is the opposite of classical growth and distinctly different than CPA. Here, we selected cholesterol as a model system based on its prevalence in physiological environments that can switch between conditions of supersaturation (crystal growth) and undersaturation (crystal dissolution). We leverage our recent observations that cholesterol nucleation and growth occur by nonclassical and classical pathways, respectively. Our findings reveal the limits of microscopic reversibility when working in moderately undersaturated solutions where dissolution occurs by a unique nonclassical pathway involving the formation of cholesterol-rich clusters on crystal surfaces. Attempts to regenerate crystal surface growth after clusters are formed reveal they have an irreversible effect on crystallization in ways that potentially inhibit pathological cholesterol precipitation.

如何引用

ACS central science 的其他文献

• 通过抗性基因引导的基因组挖掘发现的具有新作用机制的抗真菌药物