Figure 5.

Free energy and kinetic barrier analysis for penetration of amphiphilic polymer-decorated NPs. (A) (Upper part) Schematic of the solvent-accessible surface area (SASA), a parameter of the hydrophobic free energy, and electrostatic interactions; (Lower part) comparison between the initial and final stable states of the amphiphilic polymer-decorated NPs. The hydrophilic ligands are squeezed out of the bilayer’s hydrophobic region, forming a so-called “snorkeling” phenomenon; (B) Decomposition of the free energy during the NP penetration process. $\Delta G_{\text{total}}$ is the total free energy change. $\Delta G_{\text{phobic}}$ is the change of hydrophobic energy, determined through the SASA. $\Delta E_{\text{elec}}$ is the electrostatic energy change. $\Delta E_{\text{thick}}$ is the free energy change corresponding to deformation of the lipid bilayer. $\Delta S_{\text{conf}}$ is the conformation entropy change of the decorated amphiphilic polymers; (C) Total free energy change $\Delta G_{\text{total}}$ as a function of NP diameter and monolayer composition. The ligand density on the Au NPs is kept constant; (D) Snapshots of the initial and final states of the NPs interacting with a lipid bilayer. For the case of 1:1 MUS:OT NP on the top of the bilayer, it cannot penetrate into the bilayer (Upper part); while it can penetrate in the bilayer through the edge (Lower part); (E) Snapshots of the transition states during NP penetration through the edge of a bilayer. At the transition time (t = 17.66 ns), the protruding lipids were in contact with the amphiphilic NP. The figures are adapted from References [52,54,57,63] with permission.