Spontaneously translocating lipid-coated hydrophobic gold nanoparticles open doors for new biotechnology applications.

Nanoparticles (NPs) are heavily used in biomedical, industrial, and commercial applications due to the benefits associated with the specific physical and chemical properties of both the bulk and the nanoscale material. The antimicrobial activity of NPs is widely recognized, but the mechanisms of their underlying toxicity remain unclear despite repeated attempts to establish a structure-function relationship between their physicochemical properties and their interactions with biological systems. [1,2] NP uptake in mammalian cells is generally considered to be an active process, mediated by endocytosis. Indeed, transport across the cell membrane and intracellular accumulation dictates the nanoparticle fate and cytotoxicity. [3] The critical size for NPs non-disruptively (passively) crossing cellular membranes is below 10 nm, irrespective of surface functionalization, [4-7] Figure 1. For this reason, there is a slowly forming consensus that smaller NPs bear greater toxicity than larger ones. [8,9] Similarly, the antibacterial properties of small NPs have It is commonly accepted that nanoparticles (NPs) can kill bacteria; however, the mechanism of antimicrobial action remains obscure for large NPs that cannot translocate the bacterial cell wall. It is demonstrated that the increase in membrane tension caused by the adsorption of NPs is responsible for mechanical deformation, leading to cell rupture and death. A biophysical model of the NP-membrane interactions is presented which suggests that adsorbed NPs cause membrane stretching and squeezing. This general pheno menon is demonstrated experimentally using both model membranes and Pseudomonas aeruginosa and Staphylococcus aureus, representing Gram-positive and Gram-negative bacteria. Hydrophilic and hydrophobic quasi-spherical and star-shaped gold (Au)NPs are synthesized to explore the antibacterial mechanism of non-translocating AuNPs. Direct observation of nanoparticle-induced membrane tension and squeezing is demonstrated using a custom-designed microfluidic device, which relieves contraction of the model membrane surface area and eventual lipid bilayer collapse. Quasi-spherical nanoparticles exhibit a greater bactericidal action due to a higher interactive affinity, resulting in greater membrane stretching and rupturing, corroborating the theoretical model. Electron microscopy techniques are used to characterize the NP-bacterial-membrane interactions. This combination of experimental and theoretical results confirm the proposed mechanism of membrane-tension-induced (mechanical) killing of bacterial cells by non-translocating NPs.

On the basis of linear hydrodynamics, we analyze the trajectory of particle-hedgehog systems, attracted by a -1/2 disclination (defect line) in a nematic liquid crystal. We show that, as with the interactions between like-particles, the interaction between a particle and a disclination has an electrostatic analogue, the splay replacing the electric field, except for the symmetry properties. The disclination thus attracts the beads along nonradial tracks and in a self-assembling process, or template mechanism, may build a microscopic necklace with them.

Understanding how ultrasmall gold nanoparticles (metal core ∼1–1.5 nm), so-called gold nanoclusters (Au NCs), interact with biological barriers has become highly important for their future bioapplications. The properties of Au NCs with tunable hydrophobicity were extensively characterized in three different biological situations: (i) interaction with serum in solution, (ii) interaction with synthetic free-standing lipid bilayers integrated in a microfluidic device, and (iii) cell studies with two different cell types (U87MG human primary glioblastoma and A375 melanoma cell lines). Our results indicate a significant impact of the precise tailoring of the hydrophilicity/hydrophobicity balance on the Au NC surfaces, which could prevent the formation of biomolecular absorption while maintaining excellent colloidal stability in solutions with high serum contents. Increasing the surface hydrophobicity of the Au NCs enabled more efficient lipid bilayer membrane insertion and induced faster cellular uptake. We showed the existence of a hydrophobicity threshold, which resulted in colloidal instability, lipid bilayer damage, and acute cytotoxicity. We also demonstrated a significant influence of metal–ligand shell hydrophobicity on the fluorescence signal of the Au NCs, increasing it in the near-infrared region. A twofold signal enhancement was achieved by simple replacement of methyl groups with ethyl groups.