Effects of Nanoparticle Charge and Shape Anisotropy on Translocation through Cell Membranes

Abstract

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.

Lipid tail protrusions mediate the insertion of nanoparticles into model cell membranes

“…It must be emphasized that these simulations were completely unbiased; no external potential was applied to force AuNP insertion, a technique frequently used in similar simulations 22,23 that may induce unphysical system configurations.…”

“…Such amphiphilicity has already been proven to be an important factor in determining the interactions between biological nanoobjects, such as cellpenetrating peptides, and either the cell membrane or a lipid bilayer [12][13][14] . Similar interactions between monolayer-protected AuNPs and lipid bilayers have been a subject of intense investigation by experimental and theoretical studies aimed at eliciting the role of surface charge, ligand composition and particle size among other tuning parameters on nano-bio interactions 6,[15][16][17][18][19][20][21][22][23] .…”

Decoupling the shape parameter to assess gold nanorod uptake by mammalian cells

“…[38][39][40][41] This could explain the increased uptake of GNR-7.2 due to its rounded cross-section that aids membrane wrapping compared to the squarer GNR-4.8 sample. However, from TEM imaging it is evident that the concept of single non-interacting NP translocation does not occur in this study ( Fig.…”

Translational radionanomedicine: a clinical perspective

“…111 In-labeled HER-2 targeted gold nanoparticles (half-life 2.8 days) were slowly accumulated in the tumor lesions in more than 2 days (55). Because of this delayed target accumulation and excretion, long half-life radiotracers such as 67 Ga, 89 Zr, or 124 I have advantages in distribution studies. Nevertheless, because long half-life increases radiation dose, radionuclides should be selected carefully.…”

“…Particle geometry and surface charge affect the cellular internalization mediated by endocytosis. For instance, non-spherically shaped and positively charged particles let the nanoparticles to be internalized easily (66,67). Several biological factors as well as these physicochemical properties also affect in vivo distribution.…”