ER Membrane Phospholipids and Surface Tension Control Cellular Lipid Droplet Formation

Abstract

SUMMARYCells convert excess energy into neutral lipids that are made in the endoplasmic reticulum (ER) bilayer. The lipids are then packaged into spherical or budded lipid droplets (LDs) covered by a phospholipid monolayer containing proteins. LDs play a key role in cellular energy metabolism and homeostasis. A key unanswered question in the life of LDs is how they bud off from the ER. Here, we tackle this question by studying the budding of artificial LDs from model membranes. We find that the bilayer phospholipid composition and surface tension are key parameters of LD budding. Phospholipids have differential LD budding aptitudes, and those inducing budding decrease the bilayer tension. We observe that decreasing tension favors the egress of neutral lipids from the bilayer and LD budding. In cells, budding conditions favor the formation of small LDs. Our discovery reveals the importance of altering ER physical chemistry for controlled cellular LD formation.

Lipid droplet biogenesis is driven by liquid-liquid phase separation

“…We observed that increasing membrane tension antagonizes blister formation, by both decreasing its rate ( Figure 2B) and by increasing the amount of diluted TG in bilayers ( Figure 2C), in agreement with in vitro experiments 15 . Membrane curvature, on the other hand, didn't appear to affect blister formation rate ( Figure 2E), nor the chemical potential of TG molecules ( Figure 2F).…”

“…The early steps of LD biogenesis, however, remain largely unexplored and our understanding of how LDs form 3,4,[7][8][9][10][11][12] is based solely on the extrapolation of sparse experimental observations in reconstituted systems. First, micrometer-sized oil blisters have been observed during the formation of black lipid membranes 13,14 or after addition of TGs to Giant Unilamellar Vesicles 15 . Second, molecular dynamics (MD) simulations have suggested that oil lenses can form between the two bilayer leaflets when the ratio between oil and phospholipids exceeds a certain threshold 16 .…”

Arabidopsis lipid droplet‐associated protein (LDAP) – interacting protein (LDIP) influences lipid droplet size and neutral lipid homeostasis in both leaves and seeds

“…Also key to the growth of nascent LDs is the coordinated synthesis and enrichment of certain phospholipids within the LD monolayer. As such, the composition of the phospholipid monolayer is an important determinant of the size of LDs, as well as their propensity for subsequent LD-LD fusion (Thiam et al, 2013;M'barek et al, 2017). Indeed, the majority of genes identified in screens for altered LD sizes in insect and yeast cells are involved in phospholipid metabolism (Guo et al, 2008;Fei et al, 2011;Li et al, 2016;Fan et al, 2017).…”

Understanding Conformational Dynamics of Complex Lipid Mixtures Relevant to Biology

“…A recent study showed that interfacial tension of purified lipid droplets is around 2–4 mN/m, i.e., 1–2 orders of magnitude higher than that of bilayers (Ben M’barek et al. 2017). Thus, whether ST can play a role in modulating surface properties of lipid droplets was also investigated.…”

“…Lipid composition of the ER played a critical role in influencing this process (Ben M’barek et al. 2017). …”