RT Journal Article
SR Electronic
T1 Key Factors Governing Initial Stages of Lipid Droplet Formation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.12.468423
DO 10.1101/2021.11.12.468423
A1 Siyoung Kim
A1 Chenghan Li
A1 Robert V. Farese, Jr.
A1 Tobias C. Walther
A1 Gregory A. Voth
YR 2021
UL http://biorxiv.org/content/early/2021/11/13/2021.11.12.468423.abstract
AB Lipid droplets (LDs) are neutral lipid storage organelles surrounded by a phospholipid (PL) monolayer. LD biogenesis from the endoplasmic reticulum (ER) is driven by phase separation of neutral lipids, overcoming surface tension and membrane deformation. However, the core biophysics of the initial steps of LD formation remain relatively poorly understood. Here, we use a tunable, phenomenological coarse-grained (CG) model to study triacylglycerol (TG) nucleation in a bilayer membrane. We show that PL rigidity has a strong influence on TG lensing and membrane remodeling: When membrane rigidity increases, TG clusters remain more planar with high anisotropy but a minor degree of phase nucleation. This finding is confirmed by free energy sampling simulations that calculate the potential of mean force (PMF) as a function of the degree of nucleation and anisotropy. We also show that asymmetric tension, controlled by the number of PLs on each membrane leaflet, determines the budding direction. A TG lens buds in the direction of the monolayer containing excess PLs to allow for better PL coverage of TG, consistent with reported experiments. Finally, two governing mechanisms of the LD growth, Ostwald ripening and merging, are observed. Taken together, this study characterizes the interplay between two thermodynamic quantities during the initial LD phases, the TG bulk free energy and membrane remodeling energy.Competing Interest StatementThe authors have declared no competing interest.