Unveiling Interactions of Peptide-bound Monolayer Protected Metal Nanocluster with 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 nano-sized drug carriers relies on a deep understanding of their molecular-level interactions with cell membranes and other biological entities. Here, we applied coarse-grained molecular dynamics and umbrella sampling simulations to investigate the interactions between the Magainin 2 (MG2)-loaded $Au_{144}(MPA)_{60}$ nanocluster (MG2-MPC) and model anionic tumor cell membrane. Electrostatic interactions between MPC ligands and MG2's positively charged residues with the polar head groups 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.