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Nat. Commun., Published 24 June 2022 | https://doi.org/10.1038/s41467-022-31400-6 Chain flexibility of medicinal lipids determines their selective partitioning into lipid droplets

So-Hee Son^1,2, Gyuri Park³, Junho Lim⁴, Chang Yun Son^4,5,6,*, Seung Soo Oh^2,3,6,* & Ju Young Lee^1,*

¹Research Center for Bio-based Chemistry, Korea Research Institute of Chemical Technology (KRICT), 406-30, Jongga-ro, Jung-gu, Ulsan 44429, Republic of Korea. ²School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea. ³Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea. ⁴Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea. ⁵Division of Advanced Materials Science, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea. ⁶Institute for Convergence Research and Education in Advanced Technology (I-CREATE), Yonsei University, Incheon 21983, Republic of Korea.

^*Corresponding author.

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.

논문정보

형식Research article
게재일2022년 06월 (BRIC 등록일 2022-07-15)
연구진국내 연구진
분야 생명과학 > 생물공학

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