Figure 1.
Coarse-grained models of the system components.
DPPC molecule (top, left), cholesterol molecule (bottom, left), nanoparticle simulated in the water phase (center), and nanoparticle simulated in a membrane containing 30% cholesterol (right) (final snapshots). The molecules or CG beads are not shown to scale. Colors: Negative beads bearing -1e charge = purple; hydrophobic beads = cyan; positive beads = blue; cholesterol hydroxyl bead = gray; glycerol backbone beads = white; cholesterol sterol body beads = lime. The core of the NP is shown in gray and surface representation, whereas the hydrophobic parts of NP surface ligands are shown in a bead-spring representation. Arrows indicate the tendency of the surface charged ligands to associate with the DPPC head groups and their hydrophobic parts to interact with the hydrophobic core, inducing a snorkeling effect.
Figure 2.
Number density maps of the negatively charged end-terminal groups of the NP ligands.
The calculation was performed over the last 500 ns of the simulation for the different systems. The snapshots correspond to the final frame of the simulation and are depicted to indicate the relative position of the NP with respect to the lipid bilayer at the end of the simulation. White corresponds to zero density of the negatively-charged moieties, indicating the snorkeling effect, where charged-end terminal groups orient themselves towards the lipid head groups and outside of the bilayer core. A typical RGB color scale is used to show increasing occupancy. Only the NP core is shown for clarity. The coloring is the same as in Figure 1.
Figure 3.
PMF for NP partitioning in a cholesterol-free DPPC lipid bilayer.
The error bars represent standard deviations from two independent sets of Umbrella sampling calculations using the bootstrapping technique. Detailed analysis of the PMF convergence is provided in Text S1.
Figure 4.
Spatially averaged lipid order parameters for bilayer systems with different cholesterol concentrations.
The characteristic values P2 order parameter for various bilayer phases are demarcated in the color bar on the right [35]. The different box sizes are due to the gradual condensing effect of cholesterol on the bilayer.
Figure 5.
2D Radial concentration of DPPC and CHOL from the NP center of mass.
The concentration values as a function of the distance from the NP center of mass, c(d), are normalized with respect to the bulk values, cbulk.
Figure 6.
Bilayer thickness, defined as the distance between phosphate groups (PO4) of different bilayer leaflets, for different cholesterol concentrations as a function of the distance from the NP-center of mass.
Table 1.
Normalized interaction energies of the NP with the different components of the system in KJ/mol.