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The biophysics and cell biology of lipid droplets

Nature Reviews Molecular Cell Biology volume 14, pages 775–786 (2013)Cite this article

Subjects

Key Points

  • Cellular lipid droplets store lipids as reservoirs for metabolic energy and membrane precursors.

  • Lipid droplets form the dispersed phase of a cellular emulsion in the aqueous cytosol.

  • Principles of emulsion science are applicable to many lipid droplet-related processes.

  • Emulsions properties, such as lipid droplet size, are governed by surface properties of the phase interface.

  • Different lipids and proteins can modulate lipid droplet surface properties and hence lipid droplet biology.

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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Figure 1: Basic principles of emulsion physics relevant to lipid droplets.
Figure 2: Processes that govern changes in lipid droplet size.
Figure 3: Binding mode of proteins.
Figure 4: Models for mechanisms of lipid droplet formation.
Figure 5: Consumption and utilization of lipid droplets.

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Acknowledgements

The authors thank N. Bremond, F. Wilfling and F. Pincet for critical discussions on the manuscript and G. Howard for editorial assistance. Work on lipid droplets in the Walther and Farese laboratories is supported by the National Institutes of Health (NIH) grants R01GM097194 (to T.C.W.) and RO1GM099844 (to R.V.F). A.R.T. is a fellow of the Marie Curie Budding and Fusion of Lipid Droplets (BFLDs) International Outgoing Fellowships (IOF), within the 7th European Community Framework Program grant to a Partner University Funds exchange grant between the Yale and Ecole Normale Supérieure laboratories.

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Authors and Affiliations

  1. Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, 06510, Connecticut, USA

    Abdou Rachid Thiam & Tobias C. Walther

  2. Laboratoire de Physique Statistique, Ecole Normale Supérieure de Paris, Université Pierre et Marie Curie, Université Paris Diderot, Centre National de la Recherche Scientifique, 24 rue Lhomond, Paris, 75005, France

    Abdou Rachid Thiam

  3. Gladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, 94158, California, USA

    Robert V. Farese Jr

  4. Departments of Medicine and Biochemistry and Biophysics, University of California, San Francisco, 94158, California, USA

    Robert V. Farese Jr

Authors
  1. Abdou Rachid Thiam
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  2. Robert V. Farese Jr
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  3. Tobias C. Walther
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Corresponding authors

Correspondence to Robert V. Farese Jr or Tobias C. Walther.

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Glossary

Critical micellar concentration

The concentration at which surfactants form micelles.

Cosurfactants

Cosurfactants are inefficient surfactants alone and smaller than primary surfactants. They can fill the space between primary surfactants to reduce surface tension. Cosurfactants can easily partition between the different phases.

Surface tension

Surface tension (γ) reflects the energy that is required to increase the surface area of a liquid by a unit area and is the energy cost per unit area generated between two immiscible fluids. The presence of phospholipid surfactants minimizes γ by shielding the interface.

Intrinsic curvature

For a surfactant, it is their spontaneous curvature (dependent on properties such as pH, length of acyl chains and temperature). It reflects the hydrophilic and lipophilic balance of the molecules. If the mean area of the hydrophilic part of a surfactant is larger than that of the hydrophobic part, the curvature of the molecules is considered positive, and it tends to form direct micelles. In the opposite case, the curvature is negative.

Line tension

Line tension (Γ) is the energy cost per unit length at the boundary between different phases. Among many parameters, line tension is a function of surfactant acyl chain length and bending modulus.

Laplace pressure

The pressure difference (ΔP) between the inside and outside of a curved liquid surface. Surface tension compresses the disperse liquid to a spherical shape to minimize the energy of the system. Contraction arrests when a relatively positive Laplace pressure builds up inside the drop.

Permeation

In the context of emulsions it is the process by which one type of molecule (for example, triacylglycerol), which is present in one compartment, crosses a membrane barrier or a liquid film by diffusing through it and thus reaches another compartment.

Dewetting

The rupture of a thin film on a substrate to form a droplet, the counterpart to which is spreading. It depends on the surfactant concentration. Dewetting of an oil droplet within a bilayer occurs when the monolayers of the bilayer wet together. This process can be favoured in emulsions by lowering surface tension.

Contact angle

The contact angle (θ) is the angle at which a liquid interface meets a solid surface. It is also applicable to the angle between an lipid droplet and the endoplasmic reticulum bilayer.

Bending modulus

The bending modulus represents the energy that is needed to bend a monolayer from its spontaneous curvature.

Buckling interface

A 'wrinkled' surface that forms when a monolayer has become rigid because of increased phospholipid density following compression. The wrinkles are a way to relax the applied stress, as they increase the monolayer surface.

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Thiam, A., Farese Jr, R. & Walther, T. The biophysics and cell biology of lipid droplets. Nat Rev Mol Cell Biol 14, 775–786 (2013). https://doi.org/10.1038/nrm3699

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