Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Universal phase behaviors of intracellular lipid droplets.

ABSTRACT: Lipid droplets are cytoplasmic microscale organelles involved in energy homeostasis and handling of cellular lipids and proteins. The core structure is mainly composed of two kinds of neutral lipids, triglycerides and cholesteryl esters, which are coated by a phospholipid monolayer and proteins. Despite the liquid crystalline nature of cholesteryl esters, the connection between the lipid composition and physical states is poorly understood. Here, we present a universal intracellular phase diagram of lipid droplets, semiquantitatively consistent with the in vitro phase diagram, and reveal that cholesterol esters cause the liquid-liquid crystal phase transition under near-physiological conditions. We moreover combine in vivo and in vitro studies, together with the theory of confined liquid crystals, to suggest that the radial molecular alignments in the liquid crystallized lipid droplets are caused by an anchoring force at the droplet surface. Our findings on the phase transition of lipid droplets and resulting molecular organization contribute to a better understanding of their biological functions and diseases.

SUBMITTER: Shimobayashi SF

PROVIDER: S-EPMC6925986 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Lipid droplets as endogenous intracellular microlenses.

Project description:Using a single biological element as a photonic component with well-defined features has become a new intriguing paradigm in biophotonics. Here we show that endogenous lipid droplets in the mature adipose cells can behave as fully biocompatible microlenses to strengthen the ability of microscopic imaging as well as detecting intra- and extracellular signals. By the assistance of biolenses made of the lipid droplets, enhanced fluorescence imaging of cytoskeleton, lysosomes, and adenoviruses has been achieved. At the same time, we demonstrated that the required excitation power can be reduced by up to 73%. The lipidic microlenses are finely manipulated by optical tweezers in order to address targets and perform their real-time imaging inside the cells. An efficient detecting of fluorescence signal of cancer cells in extracellular fluid was accomplished due to the focusing effect of incident light by the lipid droplets. The lipid droplets acting as endogenous intracellular microlenses open the intriguing route for a multifunctional biocompatible optics tool for biosensing, endoscopic imaging, and single-cell diagnosis.

| S-EPMC8648767 | biostudies-literature

Light-Up Lipid Droplets Dynamic Behaviors Using a Red-Emitting Fluorogenic Probe.

Project description:Intracellular lipid metabolism occurs in lipid droplets (LDs), which is critical to the survival of cells. Imaging LDs is an intuitive way to understand their physiology in live cells. However, this is limited by the availability of specific probes that can properly visualize LDs in vivo. Here, an LDs-specific red-emitting probe is proposed to address this need, which is not merely with an ultrahigh signal-to-noise (S/N) ratio and a large Stokes shift (up to 214 nm) but also with superior resistance to photobleaching. The probe has been successfully applied to real-time tracking of intracellular LDs behaviors, including fusion, migration, and lipophagy processes. We deem that the proposed probe here offers a new possibility for deeper understanding of LDs-associated behaviors, elucidation of their roles and mechanisms in cellular metabolism, and determination of the transition between adaptive lipid storage and lipotoxicity as well.

| S-EPMC7307831 | biostudies-literature

Deep learning classification of lipid droplets in quantitative phase images.

Project description:We report the application of supervised machine learning to the automated classification of lipid droplets in label-free, quantitative-phase images. By comparing various machine learning methods commonly used in biomedical imaging and remote sensing, we found convolutional neural networks to outperform others, both quantitatively and qualitatively. We describe our imaging approach, all implemented machine learning methods, and their performance with respect to computational efficiency, required training resources, and relative method performance measured across multiple metrics. Overall, our results indicate that quantitative-phase imaging coupled to machine learning enables accurate lipid droplet classification in single living cells. As such, the present paradigm presents an excellent alternative of the more common fluorescent and Raman imaging modalities by enabling label-free, ultra-low phototoxicity, and deeper insight into the thermodynamics of metabolism of single cells.

| S-EPMC8021159 | biostudies-literature

Insulin activates intracellular transport of lipid droplets to release triglycerides from the liver.

Project description:Triglyceride-rich lipid droplets (LDs) are catabolized with high efficiency in hepatocytes to supply fatty acids for producing lipoprotein particles. Fasting causes a massive influx of adipose-derived fatty acids into the liver. The liver in the fasted state is therefore bloated with LDs but, remarkably, still continues to secrete triglycerides at a constant rate. Here we show that insulin signaling elevates phosphatidic acid (PA) dramatically on LDs in the fed state. PA then signals to recruit kinesin-1 motors, which transport LDs to the peripherally located smooth ER inside hepatocytes, where LDs are catabolized to produce lipoproteins. This pathway is down-regulated homeostatically when fasting causes insulin levels to drop, thus preventing dangerous elevation of triglycerides in the blood. Further, we show that a specific peptide against kinesin-1 blocks triglyceride secretion without any apparent deleterious effects on cells. Our work therefore reveals fundamental mechanisms that maintain lipid homeostasis across metabolic states and leverages this knowledge to propose a molecular target against hyperlipidemia.

| S-EPMC6829650 | biostudies-literature

Selective intracellular vaporisation of antibody-conjugated phase-change nano-droplets in vitro.

Project description:While chemotherapy is a major mode of cancer therapeutics, its efficacy is limited by systemic toxicities and drug resistance. Recent advances in nanomedicine provide the opportunity to reduce systemic toxicities. However, drug resistance remains a major challenge in cancer treatment research. Here we developed a nanomedicine composed of a phase-change nano-droplet (PCND) and an anti-cancer antibody (9E5), proposing the concept of ultrasound cancer therapy with intracellular vaporisation. PCND is a liquid perfluorocarbon nanoparticle with a liquid-gas phase that is transformable upon exposure to ultrasound. 9E5 is a monoclonal antibody targeting epiregulin (EREG). We found that 9E5-conjugated PCNDs are selectively internalised into targeted cancer cells and kill the cells dynamically by ultrasound-induced intracellular vaporisation. In vitro experiments show that 9E5-conjugated PCND targets 97.8% of high-EREG-expressing cancer cells and kills 57% of those targeted upon exposure to ultrasound. Furthermore, direct observation of the intracellular vaporisation process revealed the significant morphological alterations of cells and the release of intracellular contents.

| S-EPMC5363066 | biostudies-literature

Universal Transient Dynamics of Electrowetting Droplets.

Project description:Droplet spreading on substrates by electrowetting exhibits either of the two transient behaviours: one characterised by contact line oscillation, and the other one by slow spreading dynamics. The transition between these behaviours remains elusive due to the current limited understanding of the spreading dynamics on the hydrodynamical and electrical properties of electrowetting systems. To understand this transition we propose a model capturing the transition's occurrence based on both the hydrodynamical and electrical parameters. We derive the critical viscosity at which the transition occurs and reveal its subtle and often hidden dependence on the electrowetting dynamics. We find and experimentally verify that the condition for minimization of droplets' actuation time is only achieved at the transition. Particularly, the transition time as a function of damping ratio exhibits the general feature of Kramers' reaction-rate theory.

| S-EPMC5770462 | biostudies-literature

Consequences of motor copy number on the intracellular transport of kinesin-1-driven lipid droplets.

Project description:The microtubule motor kinesin-1 plays central roles in intracellular transport. It has been widely assumed that many cellular cargos are moved by multiple kinesins and that cargos with more motors move faster and for longer distances; concrete evidence, however, is sparse. Here we rigorously test these notions using lipid droplets in Drosophila embryos. We first employ antibody inhibition, genetics, biochemistry, and particle tracking to demonstrate that kinesin-1 mediates plus-end droplet motion. We then measure how variation in kinesin-1 expression affects the forces driving individual droplets and estimate the number of kinesins actively engaged per droplet. Unlike in vitro, increased motor number results in neither longer travel distances nor higher velocities. Our data suggest that cargos in vivo can simultaneously engage multiple kinesins and that transport properties are largely unaffected by variation in motor number. Apparently, higher-order regulatory mechanisms rather than motor number per se dominate cargo transport in vivo.

| S-EPMC2768369 | biostudies-literature

Host lipid droplets: An important source of lipids salvaged by the intracellular parasite Toxoplasma gondii.

Project description:Toxoplasma is an obligate intracellular parasite that replicates in mammalian cells within a parasitophorous vacuole (PV) that does not fuse with any host organelles. One mechanism developed by the parasite for nutrient acquisition is the attraction of host organelles to the PV. Here, we examined the exploitation of host lipid droplets (LD), ubiquitous fat storage organelles, by Toxoplasma. We show that Toxoplasma replication is reduced in host cells that are depleted of LD, or impaired in TAG lipolysis or fatty acid catabolism. In infected cells, the number of host LD and the expression of host LD-associated genes (ADRP, DGAT2), progressively increase until the onset of parasite replication. Throughout infection, the PV are surrounded by host LD. Toxoplasma is capable of accessing lipids stored in host LD and incorporates these lipids into its own membranes and LD. Exogenous addition of oleic acid stimulates LD biogenesis in the host cell and results in the overaccumulation of neutral lipids in very large LD inside the parasite. To access LD-derived lipids, Toxoplasma intercepts and internalizes within the PV host LD, some of which remaining associated with Rab7, which become wrapped by an intravacuolar network of membranes (IVN). Mutant parasites impaired in IVN formation display diminished capacity of lipid uptake from host LD. Moreover, parasites lacking an IVN-localized phospholipase A2 are less proficient in salvaging lipids from host LD in the PV, suggesting a major contribution of the IVN for host LD processing in the PV and, thus lipid content release. Interestingly, gavage of parasites with lipids unveils, for the first time, the presence in Toxoplasma of endocytic-like structures containing lipidic material originating from the PV lumen. This study highlights the reliance of Toxoplasma on host LD for its intracellular development and the parasite's capability in scavenging neutral lipids from host LD.

| S-EPMC5469497 | biostudies-literature

Universal representations of evaporation modes in sessile droplets.

Project description:In this work, we provide a simple method to represent the contact line dynamics of an evaporating sessile droplet. As a droplet evaporates, two distinct contact line dynamics are observed. They are collectively known as modes of evaporation, namely Constant Contact Radius (CCR) and Constant Contact Angle (CCA). Another intermediate mode-Stick-Slide (SS) or mixed mode is also commonly observed. In this article, we are able to provide a graphical representation to these modes (named as MOE plot), which is visually more comprehensive especially for comparative studies. In addition, the method facilitates quantitative estimation for mode of evaporation (named as MOE fraction or MOEf), which doesn't exist in literature. Thus, various substrates can now be compared based on mode of evaporation (or contact line dynamics), which are governed by fluid property and surface characteristics.

| S-EPMC5600401 | biostudies-literature

Perilipin family members preferentially sequester to either triacylglycerol-specific or cholesteryl-ester-specific intracellular lipid storage droplets.

Project description:Perilipin family proteins (Plins) coat the surface of intracellular neutral lipid storage droplets in various cell types. Studies across diverse species demonstrate that Plins regulate lipid storage metabolism through recruitment of lipases and other regulatory proteins to lipid droplet surfaces. Mammalian genomes have distinct Plin gene members and additional protein forms derived from specific mRNA splice variants. However, it is not known if the different Plins have distinct functional properties. Using biochemical, cellular imaging and flow cytometric analyses, we now show that within individual cells of various types, the different Plin proteins preferentially sequester to separate pools of lipid storage droplets. By examining ectopically expressed GFP fusions and all endogenous Plin protein forms, we demonstrate that different Plins sequester to different types of lipid droplets that are composed of either triacylcerides or cholesterol esters. Furthermore, Plins with strong association preferences to triacylceride (or cholesterol ester) droplets can re-direct the relative intracellular triacylceride-cholesterol ester balance toward the targeted lipid. Our data suggest diversity of Plin function, alter previous assumptions about shared collective actions of the Plins, and indicate that each Plin can have separate and unique functions.

| S-EPMC3482316 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data