Nanoparticles Self-Assembly within Lipid Bilayers

Abstract

Coarse-grained molecular dynamics simulations are used to model the self-assembly of small hydrophobic nanoparticles (NPs) within the interior of lipid bilayers. The simulation results reveal the conditions under which NPs form clusters and lattices within lipid bilayers of planar and spherical shapes, depending on the NP-lipid coupling strengths. The formation of nanopores within spherical bilayers with self-assembled planar NPs is also described. These observations can provide guidance in the preparation of functional bio-inorganic systems.

Figure 1

(a–d) Snapshots and close-up views of the first 84 ns of a NP inclusion process. Arrows indicate the motion of NP and lipid molecules. Initially, the NP is covered with 112 solvation lipids (R_c = 2.6), which are colored in green to distinguish them from those of the bilayer. Nearby water molecules are shown in red. (e) The inclusion time of NP with different coverages of solvation lipids. (f) A bottom view of the NP at t = 7 ns, which shows an opening of the structure due to bottom-to-top motion of lipid molecules. (g) A close-up view of the stable contact between polar head groups of the structure and those of the bilayer. This NP is solvated by 126 lipid molecules (R_c = 3.0), and it does not penetrate the bilayer within our simulation time. (h, i) Tilt angle analysis of the solvation lipid when R_c = 1.33. Normalized distributions of an azimuthal tilt angle and an angle between hydrophobic tails of POPC lipid molecules.

Figure 2

(a) Reorganization of lipid molecules in a liposome carrying 13 NPs with α = 0.5. (b–d) Stabilization of 13 NPs within a lipid bilayer: (b) α = 0.5 after 125 ns, (c) α = 1.0 after 814 ns, (d) α = 1.5 after 359 ns. (e) The height of small NP clusters, h_C(α). (f) Hexagonal arrangement of 48 hydrophobic NPs with α = 1 equilibrated in the lipid bilayer for 500 ns.

Figure 3

Stabilization of NDs with α = 1 intercalated within spherical and planar POPC bilayers. (a) Hybrid NP–liposome (d ≈ 30 nm) with 180 intercalated triangular NDs and 36 748 lipid molecules solvated in 2 669 168 water beads after 150 ns equilibration. A portion of the lipids at the top is hidden to show better the NDs organization. Representative 5 (pentagon) and 6 (hexagon) ND clusters are marked. (b) A cluster of such 6 triangular NDs inside a POPC bilayer, equilibrated for 200 ns. A color map surface is fitted to the polar heads of the lipid molecules to show the bilayer structure. (c, d) Normalized distributions of an azimuthal tilt angle and an angle between hydrophobic tails of POPC lipid molecules in the pore, ND ring, and bilayer regions, shown in (b). (e) Side view of a central portion of the pore, showing water molecules in red and polar head group of lipids in blue. (f) Fluctuations of water beads within the pore region.