Modeling nanoparticle wrapping or translocation in bilayer membranes

Abstract

The spontaneous wrapping of nanoparticles by membranes is of increasing interest as nanoparticles become more prevalent in consumer products and hence more likely to enter the human body. We introduce a simulations-based tool that can be used to visualize the molecular level interaction between nanoparticles and bilayer membranes. By combining LIME, an intermediate resolution, implicit solvent model for phospholipids, with discontinuous molecular dynamics (DMD), we are able to simulate the wrapping or embedding of nanoparticles by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer membranes. Simulations of hydrophilic nanoparticles with diameters from 10 Å to 250 Å show that hydrophilic nanoparticles with diameters greater than 20 Å become wrapped while the nanoparticle with a diameter of 10 Å does not. Instead this smaller particle became embedded in the bilayer surface where it can interact with the hydrophilic head groups of the lipid molecules. We also investigate the interaction between a DPPC bilayer and hydrophobic nanoparticles with diameters 10 Å to 40 Å. These nanoparticles do not undergo the wrapping process; instead they directly penetrate the membrane and embed themselves within the inner hydrophobic core of the bilayers.

Figure 1

(a) Coarse-grained representation of DPPC (b) Coarse-grained representation of a nanoparticle. The color scheme is; purple (choline entity – type I for DPPC site 1); yellow (phosphate group – type II for DPPC site 2); red (ester group – type III for DPPC site 3); orange (ester group – type IV for DPPC site 9); cyan (alkyl tail groups – type V for DPPC sites 4-7&10-13); green (terminal tail groups – type VI for DPPC sites 8&14); gray (nanoparticle – type VII for nanoparticle site 1). The size of the DPPC coarse-grained sites and the nanoparticle are not drawn to scale.

Figure 2

Snapshots of final configurations for simulations run on systems containing hydrophilic nanoparticles of different sizes and a DPPC bilayer membrane. Run 1 (a), 2 (b), 3 (c), 4 (d), 5 (e), 6 (f). The color scheme is: purple (DPPC choline entity), orange (DPPC phosphate group), red (DPPC ester groups), cyan (DPPC alkyl tail groups), red (nanoparticles).

Figure 2

Snapshots of final configurations for simulations run on systems containing hydrophilic nanoparticles of different sizes and a DPPC bilayer membrane. Run 1 (a), 2 (b), 3 (c), 4 (d), 5 (e), 6 (f). The color scheme is: purple (DPPC choline entity), orange (DPPC phosphate group), red (DPPC ester groups), cyan (DPPC alkyl tail groups), red (nanoparticles).

Figure 3

(a) The difference between the average z position of DPPC headgroups in square-well contact and not in square well contact with the nanoparticle versus time for Runs #1, #2 and #3. (b) A simple schematic of a DPPC bilayer interacting with a nanoparticle (red). DPPC head groups that are experiencing a square-well interaction with the nanoparticle are shown in blue whereas those in the top leaflet that are not interacting with the nanoparticle are shown in purple. The difference between the average z-position of DPPC head groups in and out of square-well contacts with the nanoparticle is calculated by taking the average z-position of the blue head groups and subtracting the average z-position of the purple head groups in the top leaflet of the bilayer. This gives us a measure of how deeply the nanoparticle has penetrated the bilayer.

Figure 4

The wrapping fraction as a function of time for nanoparticles with diameters of 20Å (Run #2), 40Å (Run #3), 60Å (Run #4), and 100Å (Run #5). The time is displayed as the time in millions of collisions.

Figure 5

Snapshots from run #3 in which a hydrophilic nanoparticle with diameter 40Å is wrapped by a bilayer membrane composed of 1500 DPPC lipids. The nanoparticle (a) reaches the surface of the bilayer at 25 million collisions. The wrapping process continues at (b) 500 million collisions, (c) 1250 million collisions and (d) 3000 million collisions.

Figure 6

Snapshots from run #8 in which a hydrophobic nanoparticle with a diameter of 20Å embeds itself in a DPPC bilayer composed of 1500 lipids. The nanoparticle (a) reaches the surface of the bilayer after 25 million collisions, (b) begins to penetrate the membrane after 50 million collisions, and (c) is fully embedded within the inner hydrophobic core of the membrane after 225 million collisions.

Figure 7

The distance from the hydrophobic nanoparticle to the plane through the bilayer center for runs #7 (10Å), #8 (20Å) #9 (30Å) and #10 (40Å). The zero time point for each run is set to the time when the nanoparticle first has a square-well interaction with a lipid tail coarse-grained site.