The biophysics and cell biology of lipid droplets
TL;DR: The regulation of the composition of the phospholipid surfactants at the surface of lipid droplets is crucial for lipid droplet homeostasis and protein targeting to their surfaces.
Abstract: Lipid droplets are intracellular organelles that are found in most cells, where they have fundamental roles in metabolism. They function prominently in storing oil-based reserves of metabolic energy and components of membrane lipids. Lipid droplets are the dispersed phase of an oil-in-water emulsion in the aqueous cytosol of cells, and the importance of basic biophysical principles of emulsions for lipid droplet biology is now being appreciated. Because of their unique architecture, with an interface between the dispersed oil phase and the aqueous cytosol, specific mechanisms underlie their formation, growth and shrinkage. Such mechanisms enable cells to use emulsified oil when the demands for metabolic energy or membrane synthesis change. The regulation of the composition of the phospholipid surfactants at the surface of lipid droplets is crucial for lipid droplet homeostasis and protein targeting to their surfaces.
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TL;DR: Lipid droplet biogenesis and degradation, as well as their interactions with other organelles, are tightly coupled to cellular metabolism and are critical to buffer the levels of toxic lipid species.
Abstract: Lipid droplets are storage organelles at the centre of lipid and energy homeostasis. They have a unique architecture consisting of a hydrophobic core of neutral lipids, which is enclosed by a phospholipid monolayer that is decorated by a specific set of proteins. Originating from the endoplasmic reticulum, lipid droplets can associate with most other cellular organelles through membrane contact sites. It is becoming apparent that these contacts between lipid droplets and other organelles are highly dynamic and coupled to the cycles of lipid droplet expansion and shrinkage. Importantly, lipid droplet biogenesis and degradation, as well as their interactions with other organelles, are tightly coupled to cellular metabolism and are critical to buffer the levels of toxic lipid species. Thus, lipid droplets facilitate the coordination and communication between different organelles and act as vital hubs of cellular metabolism.
1,143 citations
TL;DR: This work has shown that a high lipid diversity is universal in eukaryotes and is seen from the scale of a membrane leaflet to that of a whole organism, highlighting its importance and suggesting that membrane lipids fulfil many functions.
Abstract: Cellular membranes are formed from a chemically diverse set of lipids present in various amounts and proportions. A high lipid diversity is universal in eukaryotes and is seen from the scale of a membrane leaflet to that of a whole organism, highlighting its importance and suggesting that membrane lipids fulfil many functions. Indeed, alterations of membrane lipid homeostasis are linked to various diseases. While many of their functions remain unknown, interdisciplinary approaches have begun to reveal novel functions of lipids and their interactions. We are beginning to understand why even small changes in lipid structures and in composition can have profound effects on crucial biological functions.
1,012 citations
TL;DR: It is demonstrated that memory T cells rely on cell intrinsic expression of the lysosomal hydrolase LAL (lysosomal acid lipase) to mobilize FA for FAO and memory T cell development, which links LAL to metabolic reprogramming in lymphocytes and shows that cell intrinsic lipolysis is deterministic for memory Tcell fate.
601 citations
Cites background from "The biophysics and cell biology of ..."
...The Lipid Signature of Memory T Cells Suggests Active Lipolysis Most cells can store lipids as TAG and CE then subsequently release FA from these stores when needed (Thiam et al., 2013)....
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...Because intracellular free FA can be toxic, most cells store excess FA in less reactive forms, such as TAG, and then release FA from these stores as needed (Thiam et al., 2013)....
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...Most cell types are thought to be able to acquire and store excess lipids (Thiam et al., 2013)....
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...Most cells can store lipids as TAG and CE then subsequently release FA from these stores when needed (Thiam et al., 2013)....
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TL;DR: A model of LD formation from the ER in distinct steps is presented and the biology of proteins that govern this biophysical process are highlighted, as are connections with physiology and diseases linked to alterations in LD biology.
Abstract: Lipid droplets (LDs) are ubiquitous organelles that store neutral lipids for energy or membrane synthesis and act as hubs for metabolic processes. Cells generate LDs de novo, converting cells to emulsions with LDs constituting the dispersed oil phase in the aqueous cytoplasm. Here we review our current view of LD biogenesis. We present a model of LD formation from the ER in distinct steps and highlight the biology of proteins that govern this biophysical process. Areas of incomplete knowledge are identified, as are connections with physiology and diseases linked to alterations in LD biology.
544 citations
Cites background from "The biophysics and cell biology of ..."
...Above a certain size, depending on the oil and phospholipid composition, lipid lenses in the ER are predicted to be unstable and bud, by a mechanism similar to de-wetting, due to thermal fluctuations [6] (Figure 1)....
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...The generation of a large LD from two smaller LDs can occur either by direct coalescence/ fusion or by ripening (diffusion-mediated transfer of core lipids; see [6])....
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...Specific targeting signals for LD proteins are reviewed elsewhere [6,23]....
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...The surface composition is highly relevant to regulating LD size and their ability to interact with other LDs or organelles, such as the endoplasmic reticulum (ER) ([12,13] and reviewed in [6,14,15])....
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Book•
01 Jan 1978
TL;DR: In this paper, the Gibbs equation is used to calculate the area per Molecule at the interface by using the Gibbs Equation (GEE) of the Gibbs equilibrium. But the Gibbs equations are not applicable to surface-active agents.
Abstract: Preface. 1 Characteristic Features of Surfactants. A Conditions Under Which Interfacial Phenomena and Surfactants Become Significant. B General Structural Features and Behavior of Surfactants. 1 General Use of Charge Types. 2 General Effects of the Nature of the Hydrophobic Group. I Characteristic Features and Uses of Commercially Available Surfactants. I.A Anionics. 1 Carboxylic Acid Salts. 2 Sulfonic Acid Salts. 3 Sulfuric Acid Ester Salts. 4 Phosphoric and Polyphosphoric Acid Esters. 5 Fluorinated Anionics. I.B Cationics. 1 Long-Chain Amines and Their Salts. 2 Acylated Diamines and Polyamines and Their Salts. 3 Quaternary Ammonium Salts. 4 Polyoxyethylenated (POE) Long-Chain Amines. 5 Quaternized POE Long-Chain Amines. 6 Amine Oxides. I.C Nonionics. 1 POE Alkylphenols, Alkylphenol "Ethoxylates". 2 POE Straight-Chain Alcohols, Alcohol "Ethoxylates". 3 POE Polyoxypropylene glycols. 4 POE Mercaptans. 5 Long-Chain Carboxylic Acid Esters. 6 Alkanolamine "Condensates," Alkanolamides. 7 Tertiary Acetylenic Glycols and Their "Ethoxylates". 8 POE Silicones. 9 N-Alkylpyrrolidones. 10 Alkylpolyglycosides. I.D Zwitterionics. 1 pH-Sensitive Zwitterionics. 2 pH-Insensitive Zwitterionics. I.E Newer Surfactants Based Upon Renewable Raw Materials. 1 a-Sulfofatty Acid Methyl Esters (SME). 2 Acylated Aminoacids. 3 N-Acyl L-Glutamates (AG). 4 N-Acyl Glycinates. 5 N-Acyl DL-Alaninates. 6 Other Acylated Aminoacids. 7 Nopol Alkoxylates. II Environmental Effects of Surfactants. II.A Surfactant Biodegradability. II.B Surfactant Toxicity To and Bioconcentration in Marine Organisms. III Some Useful Generalizations. References. Problems. 2 Adsorption of Surface-Active Agents at Interfaces: The Electrical Double Layer. I The Electrical Double Layer. II Adsorption at the Solid-Liquid Interface. II.A Mechanisms of Adsorption and Aggregation. II.B Adsorption Isotherms. 1 The Langmuir Adsorption Isotherm. II.C Adsorption from Aqueous Solution Onto Adsorbents with Strongly Charged Sites. 1 Ionic Surfactants. 2 Nonionic Surfactants. 3 pH Change. 4 Ionic Strength. 5 Temperature. II.D Adsorption from Aqueous Solution Onto Nonpolar, Hydrophobic Adsorbents. II.E Adsorption from Aqueous Solution Onto Polar Adsorbents without Strongly Charged Sites. II.F Effects of Adsorption from Aqueous Solution on the Surface Properties of the Solid Adsorbent. 1 Substrates with Strongly Charged Sites. 2 Nonpolar Adsorbents. II.G Adsorption from Nonaqueous Solution. II.H Determination of the Specific Surface Areas of Solids. III Adsorption at the Liquid-Gas (L/G) and Liquid-Liquid (L/L) Interfaces. III.A The Gibbs Adsorption Equation 60 III.B Calculation of Surface Concentrations and Area per Molecule at the Interface By Use of the Gibbs Equation. III.C Effectiveness of Adsorption at the L/G and L/L Interfaces. III.D The Szyszkowski, Langmuir, and Frumkin Equations. III.E Efficiency of Adsorption at the L/G and L/L Interfaces. III.F Calculation of Thermodynamic Parameters of Adsorption at the L/G and L/L Interfaces. III.G Adsorption from Mixtures of Two Surfactants. References. Problems. 3 Micelle Formation by Surfactants. I The Critical Micelle Concentration (CMC). II Micellar Structure and Shape. II.A The Packing Parameter. II.B Surfactant Structure and Micellar Shape. II.C Liquid Crystals. III Micellar Aggregation Numbers. IV Factors Affecting the Value of the CMC in Aqueous Media. IV.A Structure of the Surfactant. 1 The Hydrophobic Group. 2 The Hydrophobic Group. 3 The Counterion in Ionic Surfactants: Degree of Binding to the Micelle 139 4 Empirical Equations. IV.B Electrolyte. IV.C Organic Additives. 1 Class I Materials. 2 Class II Materials. IV.D The Presence of a Second Liquid Phase. IV.E Temperature. V Micellization in Aqueous Solution and Adsorption at the Aqueous Solution-Air or Aqueous Solution-Hydrocarbon Interface. V.A. The CMC/C20 ratio. VI CMCs in Nonaqueous Media. VII Equations for the CMC Based on Theoretical Considerations. VIII Thermodynamic Parameters of Micellization. IX Mixed Micelle Formation in Mixtures of Two Surfactants. References. Problems. 4 Solubilization by Solutions of Surfactants: Micellar Catalysis. I Solubilization in Aqueous Media. I.A Locus of Solubilization. I.B Factors Determining the Extent of Solubilization. 1 Structure of the Surfactant. 2 Structure of the Solubilizate. 3 Effect of Electrolyte. 4 Effect of Monomeric Organic Additives. 5 Effect of Polymeric Organic Additives. 6 Mixed Anionic-Nonionic Micelles. 7 Effect of Temperature. 8 Hydrotropy. I.C Rate of Solubilization. II Solubilization in Nonaqueous Solvents. II.A Secondary Solubilization. III Some Effects of Solubilization. III.A Effect of Solubilization on Micellar Structure. III.B Change in the Cloud Points of Aqueous Solutions of Nonionic Surfactants. III.C Reduction of the CMC. III.D Miscellaneous Effects of Solubilization. IV Micellar Catalysis. References. Problems. 5 Reduction of Surface and Interfacial Tension by Surfactants. I Efficiency in Surface Tension Reduction. II Effectiveness in Surface Tension Reduction. II.A The Krafft Point. II.B Interfacial Parameter and Chemical Structural Effects. III Liquid-Liquid Interfacial Tension Reduction. III.A Ultralow Interfacial Tension. IV Dynamic Surface Tension Reduction. IV.A Dynamic Regions. IV.B Apparent Diffusion Coefficients of Surfactants. References. Problems. 6 Wetting and Its Modification by Surfactants. I Wetting Equilibria. I.A Spreading Wetting. 1 The Contact Angle. 2 Measurement of the Contact Angle. I.B Adhesional Wetting. I.C Immersional Wetting. I.D Adsorption and Wetting. II Modification of Wetting by Surfactants. II.A General Considerations. II.B Hard Surface (Equilibrium) Wetting. II.C Textile (Nonequilibrium) Wetting. II.D Effect of Additives. III Synergy in Wetting by Mixtures of Surfactants. IV Superspreading (Superwetting). References. Problems. 7 Foaming and Antifoaming by Aqueous Solutions of Surfactants. I Theories of Film Elasticity. II Factors Determining Foam Persistence. II.A Drainage of Liquid in the Lamellae. II.B Diffusion of Gas Through the Lamellae. II.C Surface Viscosity. II.D The Existence and Thickness of the Electrical Double Layer. III The Relation of Surfactant Chemical Structure to Foaming in Aqueous Solution. III.A Efficiency as a Foaming Agent. III.B Effectiveness as a Foaming Agent. III.C Low-Foaming Surfactants. IV Foam-Stabilizing Organic Additives. V Antifoaming. VI Foaming of Aqueous Dispersions of Finely Divided Solids. References. Problems. 8 Emulsification by Surfactants. I Macroemulsions. I.A Formation. I.B Factors Determining Stability. 1 Physical Nature of the Interfacial Film. 2 Existence of an Electrical or Steric Barrier to Coalescence on the Dispersed Droplets. 3 Viscosity of the Continuous Phase. 4 Size Distribution of Droplets. 5 Phase Volume Ratio. 6 Temperature. I.C Inversion. I.D Multiple Emulsions. I.E Theories of Emulsion Type. 1 Qualitative Theories. 2 Kinetic Theory of Macroemulsion Type. II Microemulsions. III Nanoemulsions. IV Selection of Surfactants as Emulsifying Agents. IV.A The HLB Method. IV.B The PIT Method. IV.C The HLD Method. V Demulsification. References. Problems. 9 Dispersion and Aggregation of Solids in Liquid Media by Surfactants. I Interparticle Forces. I.A Soft (electrostatic) and van der Waals Forces: DLVO Theory. 1 Limitations of the DLVO Theory. I.B Steric Forces. II Role of the Surfactant in the Dispersion Process. II.A Wetting of the Powder. II.B Deaggregation or Fragmentation of Particle Clusters. II.C Prevention of Reaggregation. III Coagulation or Flocculation of Dispersed Solids by Surfactants. III.A Neutralization or Reduction of the Potential at the Stern Layer of the Dispersed Particles. III.B Bridging. III.C Reversible Flocculation. IV The Relation of Surfactant Chemical Structure to Dispersing Properties. IV.A Aqueous Dispersions. IV.B Nonaqueous Dispersions. References. Problems. 10 Detergency and Its Modification by Surfactants. I Mechanisms of the Cleaning Process. I.A Removal of Soil from Substrate. 1 Removal of Liquid Soil. 2 Removal of Solid Soil. I.B Suspension of the Soil in the Bath and Prevention of Redeposition. 1 Solid Particulate Soils: Formation of Electrical and Steric Barriers Soil Release Agents. 2 Liquid Oily Soil. I.C Skin Irritation. I.D Dry Cleaning. II Effect of Water Hardness. II.A Builders. II.B Lime Soap Dispersing Agents. III Fabric Softeners. IV The Relation of the Chemical Structure of the Surfactant to Its Detergency. IV.A Effect of Soil and Substrate. 1 Oily Soil. 2 Particulate Soil. 3 Mixed Soil. IV.B Effect of the Hydrophobic Group of the Surfactant. IV.C Effect of the Hydrophilic Group of the Surfactant. IV.D Dry Cleaning. References. Problems. 11 Molecular Interactions and Synergism in Mixtures of Two Surfactants. I Evaluation of Molecular Interaction Parameters. I.A Notes on the Use of Equations 11.1-11.4. II Effect of Chemical Structure and Molecular Environment on Molecular Interaction Parameters. III Conditions for the Existence of Synergism. III.A Synergism or Antagonism (Negative Synergism) in Surface or Interfacial Tension Reduction Efficiency. III.B Synergism or Antagonism (Negative Synergism) in Mixed Micelle Formation in Aqueous Medium. III.C Synergism or Antagonism (Negative Synergism) in Surface or Interfacial Tension Reduction Effectiveness. III.D Selection of Surfactants Pairs for Optimal Interfacial Properties. IV The Relation between Synergism in Fundamental Surface Properties and Synergism in Surfactant Applications. References. Problems. 12 Gemini Surfactants. I Fundamental Properties. II Interaction with Other Surfactant. III Performance Properties. References. Problems. Answers to Problems. Index.
6,147 citations
TL;DR: A previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy) is identified that could have important implications for human diseases with lipid over-accumulation such as those that comprise the metabolic syndrome.
Abstract: The intracellular storage and utilization of lipids are critical to maintain cellular energy homeostasis. During nutrient deprivation, cellular lipids stored as triglycerides in lipid droplets are hydrolysed into fatty acids for energy. A second cellular response to starvation is the induction of autophagy, which delivers intracellular proteins and organelles sequestered in double-membrane vesicles (autophagosomes) to lysosomes for degradation and use as an energy source. Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. Here we show a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). Lipid droplets and autophagic components associated during nutrient deprivation, and inhibition of autophagy in cultured hepatocytes and mouse liver increased triglyceride storage in lipid droplets. This study identifies a critical function for autophagy in lipid metabolism that could have important implications for human diseases with lipid over-accumulation such as those that comprise the metabolic syndrome.
3,091 citations
TL;DR: Variation in PNPLA3 contributes to ancestry-related and inter-individual differences in hepatic fat content and susceptibility to NAFLD.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ancestry groups. To identify genetic variants contributing to differences in hepatic fat content, we carried out a genome-wide association scan of nonsynonymous sequence variations (n = 9,229) in a population comprising Hispanic, African American and European American individuals. An allele in PNPLA3 (rs738409[G], encoding I148M) was strongly associated with increased hepatic fat levels (P = 5.9 x 10(-10)) and with hepatic inflammation (P = 3.7 x 10(-4)). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was more than twofold higher in PNPLA3 rs738409[G] homozygotes than in noncarriers. Resequencing revealed another allele of PNPLA3 (rs6006460[T], encoding S453I) that was associated with lower hepatic fat content in African Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ancestry-related and inter-individual differences in hepatic fat content and susceptibility to NAFLD.
2,651 citations
01 Jan 2004
TL;DR: The first € price and the £ and $ price are net prices, subject to local VAT as discussed by the authors, and prices and other details are subject to change without notice. All errors and omissions excepted.
Abstract: The first € price and the £ and $ price are net prices, subject to local VAT. Prices indicated with * include VAT for books; the €(D) includes 7% for Germany, the €(A) includes 10% for Austria. Prices indicated with ** include VAT for electronic products; 19% for Germany, 20% for Austria. All prices exclusive of carriage charges. Prices and other details are subject to change without notice. All errors and omissions excepted. P.-G. de Gennes, F. Brochard-Wyart, D. Quere Capillarity and Wetting Phenomena
2,414 citations
Book•
08 Mar 2013
TL;DR: Capillarity: Unconstrained Interfaces / Capillarity and gravity / Hysteresis and Elasticity of Triple Lines / Wetting and Long-Range Forces b/ Hydrodynamics of Interfaces -- Thin Films, Waves, and Ripples as discussed by the authors.
Abstract: Capillarity: Unconstrained Interfaces / Capillarity and Gravity / Hysteresis and Elasticity of Triple Lines / Wetting and Long-Range Forces b/ Hydrodynamics of Interfaces -- Thin Films, Waves, and Ripples / Dynamics of the Triple Line / Dewetting / Surfactants / Special Interfaces / Transport Phenomena
1,550 citations