Fig. 2: MD simulations of lipid migration across the cytosol-to-phospholipid and phospholipid-to-TAG boundaries of LDs.
From: Chain flexibility of medicinal lipids determines their selective partitioning into lipid droplets
A, B Representative snapshots from bias-free MD simulations are visualized for (A) flexible worm-like squalene and (B) rigid rod-like zeaxanthin. The phospholipid monolayer is aligned in the xy-plane, and when initially placed in aqueous cytosol, squalene and zeaxanthin freely migrated into the LD (in the -z direction). C Relative location of the migrating lipids with respect to the phospholipid monolayer. The location of the phospholipid headgroup is set to z = 0, and the range of the monolayer is highlighted in yellow. Once both lipids touched the cytosol-to-phospholipid boundary (Interface I), they rapidly penetrated the phospholipid monolayer. However, at the phospholipid-TAG boundary (Interface II), flexible worm-like squalene migrated deeper inside the TAG matrix than the rigid rod-like zeaxanthin, which stalled at the phospholipid-TAG boundary during the 500-ns simulation. D End-to-end distance Rend-to-end during lipid migration. The length of squalene fluctuated continuously, exhibiting a wide range of sizes and shapes, whereas that of zeaxanthin remained constant due to its structural rigidity. E Estimation of friction coefficient ζ in neat TAGs obtained via steered MD simulations. Among heavily packed TAGs, worm-like squalene was subjected to twofold less frictional force than rod-like zeaxanthin. F, G Free energy landscape of (F) squalene and (G) zeaxanthin migration into cytosolic LDs, as calculated with multiwalker well-tempered metadynamics simulations. In the inset figures, the representative structures are displayed as linked with their corresponding order parameters (migration depth z and conformation order parameter μ) in the free energy landscape.
