2025-03-11 ヒューストン大学
A series of images captures how (A) thin and (B) thick cholesterol crystals grow over time inside a tiny fluid device.
<関連情報>
- https://uh.edu/news-events/stories/2025/march/03112025-rimer-vekilov-crystal-cholesterol.php
- https://www.pnas.org/doi/abs/10.1073/pnas.2415719122
コレステロール一水和物の結晶化を直接観察 Direct observation of cholesterol monohydrate crystallization
Dipayan Chakraborty, Wenchuan Ma, Xiqu, +4 , and Jeffrey D. Rimer
Proceedings of the National Academy of Sciences Published:March 3, 2025
DOI:https://doi.org/10.1073/pnas.2415719122
Significance
Cholesterol-related diseases affect a large fraction of the world’s population with significant associated health care costs, yet relatively few studies have explored mechanistic aspects of cholesterol crystallization. Here, we use alcohols as analogues of lipids to create facile environments for in situ characterization of cholesterol crystallization. Our findings reveal a classical mechanism of surface growth where interstep interactions enable a unique self-inhibition mode from merging layers that create macrosteps with much slower growth rates than those of elementary steps. These insights provide a foundation for future design of modifiers that selectively interact with crystal surfaces to cooperatively enhance growth inhibition, thus generating new opportunities to explore therapeutics that improve human health by counteracting the deleterious effects associated with cholesterol precipitation.
Abstract
Cholesterol crystallization is integral to the pathology of diseases such as atherosclerosis and gallstones, yet the relevant mechanisms of crystal growth have remained elusive. Here, we use a variety of in situ techniques to examine cholesterol monohydrate crystallization over multiple length scales. In this study, we first identified a biomimetic solvent to generate triclinic monohydrate crystals, while avoiding the formation of nonphysiological solvates and enabling crystallization at rates where the dynamics of surface growth could be captured in real time. Using a binary mixture of water and isopropanol, with the latter serving as a surrogate for lipids in physiological environments, we show that cholesterol monohydrate crystals grow classically by the nucleation and spreading of crystal layers. Time-resolved imaging confirms that layers are generated by dislocations and monomers incorporate into advancing steps after diffusion along the crystal surface and not directly from the solution. In situ atomic force microscopy (AFM) and microfluidics measurements concertedly reveal abundant macrosteps, which engender a self-inhibition mechanism that reduces the rate of crystal growth. This finding stands in contrast to numerous other systems, in which classical mechanisms lead to unhindered growth by spreading of single layers.
