Chain flexibility of medicinal lipids determines their selective partitioning into lipid droplets

So-Hee Son, Gyuri Park, Junho Lim, Chang Yun Son (), Seung Soo Oh () and Ju Young Lee ()
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So-Hee Son: Korea Research Institute of Chemical Technology (KRICT), 406-30, Jongga-ro, Jung-gu
Gyuri Park: Pohang University of Science and Technology (POSTECH)
Junho Lim: Pohang University of Science and Technology (POSTECH)
Chang Yun Son: Pohang University of Science and Technology (POSTECH)
Seung Soo Oh: Pohang University of Science and Technology (POSTECH)
Ju Young Lee: Korea Research Institute of Chemical Technology (KRICT), 406-30, Jongga-ro, Jung-gu

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31400-6

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