Antibacterial Action of Nanoparticles by Lethal Stretching of Bacterial Cell Membranes

Abstract

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.

Gold Nanoparticles: Can They Be the Next Magic Bullet for Multidrug-Resistant Bacteria?

“…For larger NPs within the size range of 80-100 nm, although they are unable to freely translocate across the bacterial cell membrane, still several studies reported their ability to eradicate bacteria [41][42][43][44][45]. The exact antibacterial mechanism of action for larger NPs remained somewhat obscure, until in a recent study [46] researchers provided evidence for what is known as the mechano-bactericidal mechanism of non-translocating NPs. Their work demonstrated that an increase in the membrane tension of bacterial cells is caused by the adsorption of NPs leading to mechanical deformation of the membrane, and eventually cell rupture and death.…”

“…The concept behind this approach is in designing antibacterial nanomaterials, with a specific nanostructure geometry capable of applying deadly mechanical forces to bacterial cells upon contact. This technique was applied in a recent study [46] for quasi-spherical and star-shaped AuNPs, where quasi-spherical nanoparticles showed a better bactericidal action due to a higher interactive affinity, causing greater membrane stretching and rupturing.…”

“…The APTT depends on the shape and the structure of the particles, and if they are aggregated or not [61]. Gold nanorods (AuNRs) and nanostars (AuNSTs) are two famous examples used in the APTT approach for biofilm eradication [44,46,58].…”

Protein corona modulates interaction of spiky nanoparticles with lipid bilayers

“…Figure 2: A) Schematic illustration of the bilayer formation from a mixture of lipid+oil (DOPC + Squalene) sandwiched between two water droplets: the bilayer forms after drainage of the oil, in 10-15 minutes. 35,36 The resulting bilayer is stable for at least ≈ 0.5 -2 hours. B) Visualization under dark-field microscopy of an horizontal lipid bilayer in the presence of spiky nanoparticles (100 nm diameter).…”

Nanoplatforms for Sepsis Management: Rapid Detection/Warning, Pathogen Elimination and Restoring Immune Homeostasis

“…By taking advantage of proper surface chemistry and inherent nanoplasmonic effect, Au-based nanoplatforms achieved photobactericidal activity against both Gram-negative and Gram-positive bacteria through producing ROS [ 183 ]. In fact, AuNPs can directly kill bacteria ( e.g., Pseudomonas aeruginosa and Staphylococcus aureus ) through inducing lethal bacterial membrane-tension alterations [ 184 ]. One of the most representational nanomaterials with intrinsic antibacterial activity is AgNPs which can eradicate broad-spectrum bacteria even including multidrug-resistant strains and have already been developed as antimicrobial dressings for wound management [ 185 , 186 ].…”