Energy Barrier of a Monolayer Stalk Formation during Lipid Droplet Fusion

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Abstract

Lipid droplets are organelles responsible for the accumulation and breakdown of neutral fats in the human body. Lipid droplets have a monolayer shell of phospholipids, which prevents their spontaneous fusion. The fusion of lipid droplets is carried out by specialized fusion proteins and is regulated by the lipid composition of the monolayer membrane. The efficiency of fusion is determined by the energy needed for the local approach of lipid droplets and the topological rearrangement of their monolayers. In this work, the fusion of monolayers is modeled within the framework of the theory of membrane elasticity. The energy barrier for fusion is calculated under various conditions simulating possible compositions of monolayers, as well as the possible effects of proteins. The calculation results show that the height of the barrier is most dependent on the distance between lipid droplets, which is determined by the fusion proteins. Lipid composition also affects the fusion efficiency and can change it several tens of times, which is consistent with previously obtained data on bilayer fusion.

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About the authors

R. J. Molotkovsky

Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences

Author for correspondence.
Email: rodion.molotkovsky@gmail.com
Russian Federation, Moscow, 119071

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2. Fig. 1. Schematic representation of the monolayer fusion process. a - Initial state: two flat monolayers are at a distance H0 from each other. b - Formation of local symmetric bulges at a distance d. c - Formation of monolayer stalk, i.e. dense contact of membranes with each other.

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3. Fig. 2. Models of intermediate stages of monolayer fusion. a - Local bulges of radius R located at a distance d from each other. b - Monolayers with hydrophobic defects. The distance between membranes at r → ∞ is equal to H0 and does not change during fusion.

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4. Fig. 3. Dependence of the total bulge energy Wtot1 (panel a) and defect energy Wtot2 (panel b) on the radius R at fixed values of the distance d between monolayers. The red curves correspond to d = 1 nm, the blue curves correspond to d = 0.8 nm, and the green curves correspond to d = 0.6 nm. The other parameters of the system have the following values: H0 = 3 nm, P0 = 800 kBT/nm3, ξh = 0.2 nm, ξp = 1 nm, Js = -0.1 nm-1, KG = -5 kBT, Kt = 10 kBT/nm2, l = 1 nm, σp = 12.5 kBT /nm2, σ = 0.05 kBT /nm2.

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5. Fig. 4. Energy trajectory of monolayer fusion in (H0 - d, W) coordinates. The beginning of the fusion is on the left and corresponds to the absence of bulges; the end of the trajectory is on the right and corresponds to the formation of a monolayer stalk (d = 0). The equilibrium energy of bulges Wtot1 is shown in red; the equilibrium energy of monolayers with hydrophobic defects Wtot2 is shown in blue. The system parameters are the same as in Fig. 3.

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6. Fig. 5. Dependence of the barrier height on the formation of monolayer EBarr stalk (kBT) on H0 for monolayers of different compositions and at different values of the Gaussian curvature modulus KG. Dependences for monolayers made of pure DOPC are shown in red, blue - for monolayers of composition DOPC : DOPE = 3:1, green - for monolayers of composition DOPC : DOPE = 1:1. Solid lines show the dependences for the case KG = -8 kBT, dashed lines - for the case KG = -5 kBT. The values of elastic moduli and spontaneous curvature for monolayers of different compositions are given in Table 1.

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