Interfacial properties of high-density lipoprotein-like lipid droplets with different lipid and apolipoprotein A-I compositions

Abstract

The surface properties of high-density lipoproteins (HDLs) are important because different enzymes bind and carry out their functions at the surface of HDL particles during metabolic processes. However, the surface properties of HDL and other lipoproteins are poorly known because they cannot be directly measured for nanoscale particles with contemporary experimental methods. In this work, we carried out coarse-grained molecular dynamics simulations to study the concentration of core lipids in the surface monolayer and the interfacial tension of droplets resembling HDL particles. We simulated lipid droplets composed of different amounts of phospholipids, cholesterol esters (CEs), triglycerides (TGs), and apolipoprotein A-Is. Our results reveal that the amount of TGs in the vicinity of water molecules in the phospholipid monolayer is 25-50% higher compared to the amount of CEs in a lipid droplet with a mixed core of an equal amount of TG and CE. In addition, the correlation time for the exchange of molecules between the core and the monolayer is significantly longer for TGs compared to CEs. This suggests that the chemical potential of TG is lower in the vicinity of aqueous phase but the free-energy barrier for the translocation between the monolayer and the core is higher compared to CEs. From the point of view of enzymatic modification, this indicates that TG molecules are more accessible from the aqueous phase. Further, our results point out that CE molecules decrease the interfacial tension of HDL-like lipid droplets whereas TG keeps it constant while the amount of phospholipids varies.

Figure 1

Radial density profiles showing the distribution of core and surface lipids in lipid droplet simulations S0-S8 (above). (Black refers to POPC, red to CE, and purple to TG.) Snapshots from the end of simulations of S5 and S7 to visualize the distribution of core lipids in lipid droplets when surface pressure is increased (bottom). (Left simulation snapshots) Slice from the center of particles. (Right snapshots) Surface of droplets. (Gray sticks) POPC molecules. (Blue spheres) NC3 beads. (Red) Cholesterol esters. (Indigo) Triglycerides. (Green spheres) GLY (TG) beads. (Yellow spheres) ES (CE) beads. For clarity, the water beads were removed from the snapshots.

Figure 2

Number of contacts between core lipid ES (CE) or GLY (TG) beads and water beads. The standard deviations for the number of contacts are two.

Figure 3

Order parameters for POPC acyl chains in simulations S1–S6, SP2, and SP4. (Black lines) Pure lipid droplet simulations. (Red lines) Simulations in which apo A-Is are also present.

Figure 4

Pressure profiles for lipid droplets in simulations: S1–S3, S5–S7, S0, S4, S8, SP2, and SP4. (Black lines) Transverse p_T(r). (Red lines) Normal p_rr(r) components of the pressure. (Black points) POPC density maxima, which are taken from the data in Fig. 1.

Figure 5

Autocorrelation functions for the contacts between W-ES (black or red) and W-GLY (purple) beads.