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Liquid-crystalline phase transitions in lipid droplets are related to cellular states and specific organelle association.

ABSTRACT: Lipid droplets (LDs) are ubiquitous organelles comprising a central hub for cellular lipid metabolism and trafficking. This role is tightly associated with their interactions with several cellular organelles. Here, we provide a systematic and quantitative structural description of LDs in their native state in HeLa cells enabled by cellular cryoelectron microscopy. LDs consist of a hydrophobic neutral lipid mixture of triacylglycerols (TAG) and cholesteryl esters (CE), surrounded by a single monolayer of phospholipids. We show that under normal culture conditions, LDs are amorphous and that they transition into a smectic liquid-crystalline phase surrounding an amorphous core at physiological temperature under certain cell-cycle stages or metabolic scenarios. Following determination of the crystal lattice spacing of 3.5 nm and of a phase transition temperature below 43 °C, we attributed the liquid-crystalline phase to CE. We suggest that under mitotic arrest and starvation, relative CE levels increase, presumably due to the consumption of TAG metabolites for membrane synthesis and mitochondrial respiration, respectively, supported by direct visualization of LD-mitochondrial membrane contact sites. We hypothesize that the structural phase transition may have a major impact on the accessibility of lipids in LDs to enzymes or lipid transporters. These may become restricted in the smectic phase, affecting the exchange rate of lipids with surrounding membranes and lead to a different surface occupancy of LD-associated proteins. Therefore, the composition and the resulting internal structure of LDs is expected to play a key role in their function as hubs of cellular lipid flux.

SUBMITTER: Mahamid J

PROVIDER: S-EPMC6708344 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Liquid-crystalline phase transitions in lipid droplets are related to cellular states and specific organelle association.

Mahamid Julia J Tegunov Dimitry D Maiser Andreas A Arnold Jan J Leonhardt Heinrich H Plitzko Jürgen M JM Baumeister Wolfgang W

Proceedings of the National Academy of Sciences of the United States of America 20190802 34

Lipid droplets (LDs) are ubiquitous organelles comprising a central hub for cellular lipid metabolism and trafficking. This role is tightly associated with their interactions with several cellular organelles. Here, we provide a systematic and quantitative structural description of LDs in their native state in HeLa cells enabled by cellular cryoelectron microscopy. LDs consist of a hydrophobic neutral lipid mixture of triacylglycerols (TAG) and cholesteryl esters (CE), surrounded by a single mono ...[more]

PMID: 31375636

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Project description:We report an investigation of ordering transitions that are induced in water-dispersed, micrometer-sized droplets of a thermotropic liquid crystal (LC) by the bacterial lipopolysaccharide endotoxin. We reveal that the ordering transitions induced by endotoxin - from a bipolar state of the droplets to a radial state - are strongly dependent on the size of the LC droplets. Specifically, as the diameters of the LC droplets increase from 2 μm to above 10 μm (in phosphate buffered saline with an ionic strength of 90 mM and a pH of 7.2), we measured the percentage of droplets exhibiting a radial configuration in the presence of 100 pg/mL endotoxin to decrease from 98 ± 1 % to 3 ± 2 %. In addition, we measured a decrease in either the ionic strength or pH of the aqueous phase to reduce the percentage of droplets exhibiting a radial configuration in the presence of endotoxin. These results, when interpreted within the context of a simple thermodynamic model that incorporates the contributions of elasticity and surface anchoring to the free energies of the LC droplets, lead us to conclude that (i) the elastic constant K24 plays a central role in determining the size-dependent response of the LC droplets to endotoxin, and (ii) endotoxin-triggered ordering transitions occur only under solution conditions (pH, ionic strength) where the combined contributions of elasticity and surface anchoring to the free energies of the bipolar and radial configurations of the LC droplets are similar in magnitude. Our analysis also suggests that the presence of endotoxin perturbs the free energies of the LC droplets by ~10-17 J/droplet, which is comparable to the standard free energy of self-association of ~103 endotoxin molecules. These results, when combined with prior reports of localization of endotoxin at the center of LC droplets, are consistent with the hypothesis that self-assembly of endotoxin within micrometer-sized LC droplets provides the driving force for the ordering transitions. Overall, these results advance our understanding of ordering transitions triggered by the interactions of analytes with LC droplets and, more broadly, provide guidance to the design of LC droplet systems as the basis of stimuli-responsive soft materials.

Dataset Information

Liquid-crystalline phase transitions in lipid droplets are related to cellular states and specific organelle association.

Publications

Liquid-crystalline phase transitions in lipid droplets are related to cellular states and specific organelle association.

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