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Chain flexibility of medicinal lipids determines their selective partitioning into lipid droplets
Nature Communications ( IF 14.7 ) Pub Date : 2022-06-24 , DOI: 10.1038/s41467-022-31400-6
So-Hee Son 1, 2 , Gyuri Park 3 , Junho Lim 4 , Chang Yun Son 4, 5, 6 , Seung Soo Oh 2, 3, 6 , Ju Young Lee 1
Affiliation  

In guiding lipid droplets (LDs) to serve as storage vessels that insulate high-value lipophilic compounds in cells, we demonstrate that chain flexibility of lipids determines their selective migration in intracellular LDs. Focusing on commercially important medicinal lipids with biogenetic similarity but structural dissimilarity, we computationally and experimentally validate that LD remodeling should be differentiated between overproduction of structurally flexible squalene and that of rigid zeaxanthin and β-carotene. In molecular dynamics simulations, worm-like flexible squalene is readily deformed to move through intertwined chains of triacylglycerols in the LD core, whereas rod-like rigid zeaxanthin is trapped on the LD surface due to a high free energy barrier in diffusion. By designing yeast cells with either much larger LDs or with a greater number of LDs, we observe that intracellular storage of squalene significantly increases with LD volume expansion, but that of zeaxanthin and β-carotene is enhanced through LD surface broadening; as visually evidenced, the outcomes represent internal penetration of squalene and surface localization of zeaxanthin and β-carotene. Our study shows the computational and experimental validation of selective lipid migration into a phase-separated organelle and reveals LD dynamics and functionalization.



中文翻译:

药用脂质链的柔韧性决定了它们选择性地分配成脂滴

在引导脂滴 (LD) 作为储存容器隔离细胞中高价值亲脂性化合物的过程中,我们证明了脂质链的柔韧性决定了它们在细胞内 LD 中的选择性迁移。着眼于具有生物遗传相似性但结构不同的商业上重要的药用脂质,我们通过计算和实验验证了 LD 重塑应该在结构灵活的角鲨烯和刚性玉米黄质和 β-胡萝卜素的过量生产之间进行区分。在分子动力学模拟中,蠕虫状柔性角鲨烯很容易变形以穿过 LD 核心中交织的三酰甘油链,而棒状刚性玉米黄质由于扩散中的高自由能垒而被困在 LD 表面。通过设计具有更大 LD 或具有更多 LD 的酵母细胞,我们观察到角鲨烯的细胞内储存随着 LD 体积膨胀而显着增加,但玉米黄质和β-胡萝卜素的储存通过 LD 表面增宽而增强;从视觉上可以看出,结果代表角鲨烯的内部渗透以及玉米黄质和 β-胡萝卜素的表面定位。我们的研究显示了选择性脂质迁移到相分离细胞器中的计算和实验验证,并揭示了 LD 动力学和功能化。结果代表角鲨烯的内部渗透和玉米黄质和β-胡萝卜素的表面定位。我们的研究显示了选择性脂质迁移到相分离细胞器中的计算和实验验证,并揭示了 LD 动力学和功能化。结果代表角鲨烯的内部渗透和玉米黄质和β-胡萝卜素的表面定位。我们的研究显示了选择性脂质迁移到相分离细胞器中的计算和实验验证,并揭示了 LD 动力学和功能化。

更新日期:2022-06-24
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