Effects of nanoparticle charge and shape anisotropy on translocation through cell membranes

Nanotoxicity is becoming a major concern as the use of nanoparticles in imaging, therapeutics, diagnostics, catalysis, sensing, and energy harvesting continues to grow dramatically. The tunable functionalities of the nanoparticles offer unique chemical interactions in the translocation process through cell membranes. The overall translocation rate of the nanoparticle can vary immensely on the basis of the charge of the surface functionalization along with shape and size. Using advanced molecular dynamics simulation techniques, we compute translocation rate constants of functionalized cone-, cube-, rod-, rice-, pyramid-, and sphere-shaped nanoparticles through lipid membranes. The computed results indicate that depending on the nanoparticle shape and surface functionalization charge, the translocation rates can span 60 orders of magnitude. Unlike isotropic nanoparticles, positively charged, faceted, rice-shaped nanoparticles undergo electrostatics-driven reorientation in the vicinity of the membrane to maximize their contact area and translocate instantaneously, disrupting lipid self-assembly and thereby causing significant membrane damage. In contrast, negatively charged nanoparticles are electrostatically repelled from the cell membrane and are less likely to translocate. Differences in translocation rates among various shapes may have implications on the structural evolution of pathogens from spherical to rodlike morphologies for enhanced efficacy.