Encapsulation of nanoparticles functionalized with ligands and peptides into protein cages

Experiments have shown the gold nanoparticles (NPs) densely decorated with short positively-charged ligands and sparsely decorated by longer uncharged cargo-loading peptides (CLPs) could be encapsulated into negatively-charged encapsulin protein cages with high efficiency. To investigate the underlying mechanisms driving this encapsulation, we developed a coarse-grained molecular dynamics simulation with explicit ions and water. Based on the potential of mean force between the NP and encapsulin protomers, the attraction was found to steadily decrease with increasing salt concentration, consistent with experiments. PMFs show a longer-range attraction between NPs and protomers for NPs grafted with CLPs, revealing that the CLPs expand the NP's recruitment zone, increasing the likelihood of protomer capture. Once the protomer enters the recruitment zone, however, the attractive force between protomer and NP were found to be comparable with or without CLPs, suggesting that the electrostatic attraction is the dominant driving force for encapsulation. These findings reveal a synergistic effect between the CLPs and ligands in enhancing the NP's ability to recruit protomers that results in the encapsulation as a favorable co-assembly product.