Effect of Nanoparticles on the Bulk Shear Viscosity of a Lung Surfactant Fluid

Abstract

Inhaled nanoparticles (< 100 nm) reaching the deep lung region first interact with the pulmonary surfactant, a thin lipid film lining the alveolar epithelium. To date, most biophysical studies have focused on particle induced modifications of the film interfacial properties. In comparison, there is less work on the surfactant bulk properties, and on their changes upon particle exposure. Here we study the viscoelastic properties of a biomimetic pulmonary surfactant in the presence of various engineered nanoparticles. The microrheology technique used is based on the remote actuation of micron-sized wires via the application of a rotating magnetic field and on timelapse optical microscopy. It is found that particles strongly interacting with lipid vesicles, such as cationic silica (SiO2, 42 nm) and alumina (Al2O3, 40 nm) induce profound modifications of the surfactant flow properties, even at low concentrations. In particular, we find that silica causes fluidification, while alumina induces a liquid-to-soft solid transition. Both phenomena are described quantitatively and accounted for in the context of colloidal physics models. It is finally suggested that the structure and viscosity changes could impair the fluid reorganization and recirculation occurring during breathing.

Pulmonary surfactant inhibition of nanoparticle uptake by alveolar epithelial cells

“…The silica nanoparticle-Curosurf dispersion at was investigated using TEM. This mixing ratio is smaller than the estimated mixing ratio in occupational exposure which is of the order of 10 4 29 . Despite such difference, a lower mixing ratio was used to provide sufficient nanoparticle density for TEM observations.…”

“…We note that X = 2 exposure condition corresponds to the peak of light scattering intensity of dispersions signifying a mixing ratio where the interactions result in largest aggregates 26 . The condition X = 20 is closer to the estimated mixing ratio in the lungs 29 . The results of these DLS measurements are presented in S8.…”

“…Other non-specific interactions leading to disintegration, reduction in size, and deformation of multivesicular structures have been observed with titanium oxide nanoparticles at in vivo surfactant concentration 28 . These interactions can change the biophysical properties of surfactant as recently shown in case of its flow properties 29 .…”

“…While the exposed mass is in agreement with the estimated daily lung burden previously discussed, the surface concentration is an overestimation. In fact, recapitulating the large surface area of alveolar region (70 m 2 ) 5 is not possible in vitro, and further lowering the concentration of nanoparticles may prone them to be undetectable 29 . Thereby our results present a high nanoparticle burden scenario and the effect of surfactant in alleviating such extreme condition.…”

Magnetic wire active microrheology of human respiratory mucus

“…42,43 We use microrheology platform called magnetic rotational spectroscopy (MRS) based on the time-lapse microscopy tracking of magnetically actuated micron-sized wires. [44][45][46][47][48] Ex Vivo mucus samples are collected from human bronchus tube after surgery or from the culture of human bronchus tissue. The collected volumes in the former are in the milliliter range, while the volumes secreted in the latter case are in the range of 10 -30 µl, which is sufficient for MRS. Wires of length 5 -80 µm, i.e.…”