Polyelectrolyte stiffness on gold nanorods mediates cell membrane damage

Charge and surface chemistry of gold nanorods (AuNRs) are often considered the predictive factors for cell membrane damage. Unfortunately, extensive research on AuNR passivated with polyelectrolyte (PE) ligand shell (AuNR-PE) has hitherto left a vital knowledge gap between the mechanical stability of the ligand shell and the cytotoxicity of AuNR-PEs. Here, the agreement between unbiased coarse-grained molecular dynamics (CGMD) simulation and empirical outcomes on hemolysis of red blood cells by AuNR-PEs demonstrates for the first time, a direct impact of the mechanical stability of the PE shell passivating the AuNRs on the lipid membrane rupture. Such mechanical stability is ultimately modulated by the rigidity of the PE components. The CGMD simulation results also reveal the mechanism where the PE chain adsorbs near the surface of the lipid bilayer without penetrating the hydrophobic core of the bilayer, which allows the hydrophobic AuNR core to be in direct contact with the hydrophobic interior of the lipid bilayer, thereby perforating the lipid membrane to induce membrane damage.