Biomechanical effects of environmental and engineered particles on human airway smooth muscle cells

Abstract

The past decade has seen significant increases in combustion-generated ambient particles, which contain a nanosized fraction (less than 100 nm), and even greater increases have occurred in engineered nanoparticles (NPs) propelled by the booming nanotechnology industry. Although inhalation of these particulates has become a public health concern, human health effects and mechanisms of action for NPs are not well understood. Focusing on the human airway smooth muscle cell, here we show that the cellular mechanical function is altered by particulate exposure in a manner that is dependent upon particle material, size and dose. We used Alamar Blue assay to measure cell viability and optical magnetic twisting cytometry to measure cell stiffness and agonist-induced contractility. The eight particle species fell into four categories, based on their respective effect on cell viability and on mechanical function. Cell viability was impaired and cell contractility was decreased by (i) zinc oxide (40 -100 nm and less than 44 mm) and copper(II) oxide (less than 50 nm); cell contractility was decreased by (ii) fluorescent polystyrene spheres (40 nm), increased by (iii) welding fumes and unchanged by (iv) diesel exhaust particles, titanium dioxide (25 nm) and copper(II) oxide (less than 5 mm), although in none of these cases was cell viability impaired. Treatment with hydrogen peroxide up to 500 mM did not alter viability or cell mechanics, suggesting that the particle effects are unlikely to be mediated by particle-generated reactive oxygen species. Our results highlight the susceptibility of cellular mechanical function to particulate exposures and suggest that direct exposure of the airway smooth muscle cells to particulates may initiate or aggravate respiratory diseases.

A review of mammalian toxicity of ZnO nanoparticles

“…56 Both 40-100 nm ZnO NPs and 44 µm micro-sized ZnO particles decreased viability and cell contractility of human airway smooth muscle cells. 57 It may be speculated that ZnO NPs mediate UV phototoxicity. However, at least in vitro there was no difference in cytotoxicity between UV-irradiated and nonirradiated ZnO NPs.…”

Endocytosis of Environmental and Engineered Micro‐ and Nanosized Particles

“…However, direct interaction of NPs with key functional cells may possibly result in even more potent functional changes as it has been described by Berntsen et al (7). These authors described the susceptibility of cellular mechanical functions to different particulate exposures.…”

“…Another recent study brought evidence for susceptibility of mechanical functions of smooth muscle cells to exposure of particulates (7).…”

Vibrational Spectroscopy: Disease Diagnostics and Beyond

“…However, they fail to provide a verification of nanoparticle internalisation or elucidate intracellular trafficking mechanisms and subcellular distribution within cells. Indeed, false positive results have been demonstrated due to the extracellular interaction of the nanoparticles with the cell culture medium in vitro, and with the cytotoxic assays themselves [152,152]. The underlying principles of internalisation and distribution of nano-particles within cells and any associated toxicity to humans are still relatively poorly understood.…”