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- Title
Chain flexibility of medicinal lipids determines their selective partitioning into lipid droplets.
- Authors
Son, So-Hee; Park, Gyuri; Lim, Junho; Son, Chang Yun; Oh, Seung Soo; Lee, Ju Young
- Abstract
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. Lipid droplet (LD) is a highly dynamic organelle capable of regulating lipid metabolism, storage and transportation. Here, by combining molecular dynamics simulations and microbial LD engineering, the authors demonstrate that the structural flexibility of lipids is one of decisive factors in selective partitioning into LDs.
- Subjects
ZEAXANTHIN; MOLECULAR dynamics; LIPIDS; LIPID metabolism; ACTIVATION energy
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-31400-6