Specific and nondisruptive interaction of guanidium-functionalized gold nanoparticles with neutral phospholipid bilayers

Guanidinium-containing macromolecules, such as arginine-rich peptides, have peculiar properties in their interactions with membranes, including efficient translocation. Here the authors show that cationic gold nanoparticles functionalized with guanidinium groups can specifically and nondisruptively interact with phospholipid bilayer membranes. Understanding and controlling the interaction between nanoparticles and biological entities is fundamental to the development of nanomedicine applications. In particular, the possibility to realize nanoparticles capable of directly targeting neutral lipid membranes would be advantageous to numerous applications aiming at delivering nanoparticles and their cargos into cells and biological vesicles. Here, we use experimental and computational methodologies to analyze the interaction between liposomes and gold nanoparticles (AuNPs) featuring cationic headgroups in their protecting monolayer. We find that in contrast to nanoparticles decorated with other positively charged headgroups, guanidinium-coated AuNPs can bind to neutral phosphatidylcholine liposomes, inducing nondisruptive membrane permeabilization. Atomistic molecular simulations reveal that this ability is due to the multivalent H-bonding interaction between the phosphate residues of the liposome's phospholipids and the guanidinium groups. Our results demonstrate that the peculiar properties of arginine magic, an effect responsible for the membranotropic properties of some naturally occurring peptides, are also displayed by guanidinium-bearing functionalized AuNPs.

Automated summary

The study demonstrates that cationic gold nanoparticles functionalized with guanidinium groups can interact specifically and nondisruptively with phospholipid bilayer membranes, inducing membrane permeabilization by multivalent H-bonding interactions. These findings suggest potential applications for delivering nanoparticles and their cargos into cells and biological vesicles.