posted on 2022-01-06, 22:34authored bySiyoung Kim, Chenghan Li, Robert V. Farese, Tobias C. Walther, Gregory A. Voth
Lipid
droplets (LDs) are neutral lipid storage organelles surrounded
by a phospholipid (PL) monolayer. LD biogenesis from the endoplasmic
reticulum 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 remains relatively poorly understood.
Here, we use a tunable, phenomenological coarse–grained 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 advanced sampling simulations that calculate
nucleation free energy as a function of the degree of nucleation and
anisotropy. We also show that asymmetric tension, controlled by the
number of PL molecules on each membrane leaflet, determines the budding
direction. A TG lens buds in the direction of the monolayer containing
excess PL molecules to allow for better PL coverage of TG, consistent
with the 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.