Unveiling Interactions of a Peptide-Bound Monolayer-Protected Metal Nanocluster with a Lipid Bilayer

Monolayer-protected atomically precise nanoclusters (MPCs) are potential candidates for drug delivery because of their unique, versatile, and tunable physiochemical properties. The rational design of nanosized drug carriers relies on a deep understanding of their molecular-level interactions with cell membranes and other biological entities. In this work, we applied coarse-grained molecular dynamics and umbrella sampling simulations to investigate the interactions between the magainin 2 (MG2)-loaded Au144(MPA)60 (MPA = 5-mercaptopentanoic acid) nanocluster (MG2-MPC) and a model anionic tumor cell membrane. Electrostatic interactions between MPC ligands and MG2's positively charged residues with the polar headgroups of lipids play a crucial role in the adhesion of the MG2-MPC complex to the membrane surface. Furthermore, MG2-MPCs self-assemble in the linear trimeric supramolecular aggregate on the bilayer surface, indicating a possible mechanism of MPC's action in peptide delivery to the membrane.