To determine the mechanisms of peptide encapsulation in the two different locations within the NP, we investigated the interactions of the EEK molecules with the polymer blocks and water (Figure , see SI for full methodology details). Figure (a) shows that EEK peptides inside the core are generally less hydrated than the peptides on the surface, as expected. As we detailed previously, there is a small amount of water close to the NP core center, so the peptides within the core do still interact with water. The polymer blocks do not completely shield EEK from water, in agreement with previous computational studies of peptide solubilization by polymers. EEK and all polymer beads at the core center and the core-corona interface. In the core center, most peptide residues exhibit a greater number of contacts with polymers than those peptides at the core-shell interface as might reasonably be expected. ALA and LYS residues of core residing peptides have the fewest polymer contacts but are the most heavily hydrated. So for peptides in the core center, these residues are most commonly found to be in contact with the small water nucleus in the NP core.