Protonation-dependent adsorption of polyarginine onto silver nanoparticles

Polyarginine (poly-Arg) and arginine-rich peptides have been attracting enormous interest in chemical and cell biology as cell-penetrating peptides capable of direct intracellular penetration. Owing to advances in protein engineering, arginine-rich fragments are often incorporated into multifunctional bioorganic/inorganic core–shell nanoparticles, enabling them the novel unique ability to cross cells and deliver biopharmaceutical cargos. Therefore, understanding the molecular details of the adsorption, packing, and release of poly-Arg onto or from metal nanoparticles is one of the current challenges. In this work, we carry out atomistic molecular dynamics simulations to identify the most favorable location, orientation, and conformation of poly-Arg adsorbed onto a silver nanoparticle (AgNP). Herein, we utilize the constant protonation approach to identify the role of protonation of side chain arginine moieties in the adsorption of poly-Arg to AgNP as a function of pH. The strong adsorption of unprotonated poly-Arg30 onto the quasispherical surface of AgNP with an average diameter of 3.9 nm is primarily governed by multiple interactions of side chain guanidinium (Gdm) moieties, which get stacked and align flat onto the surface. The protonation of the arginine side chain enhances the protein–solvent interactions and promotes the weakening of the protein–nanoparticle binding. The formation of multiple H-bonds between the protonated Arg residues and water molecules favors exposing the charged Gdm+ moieties to the solvent. Protonated poly-Arg30 is found to be partially bound to AgNP due to some weak protein–nanoparticle contacts, maintained by binding of the amide oxygen atoms of the peptide bond. These results suggest that reversible acid–base switching between the arginine protonation states is able to drive the rearrangement of the polyarginine coating around AgNPs, which could be important for a rational design of “intelligent” multifunctional core–shell nanosystems.