[Paper Review] Effect of Nanoparticles on the Bulk Shear Viscosity of a Lung Surfactant Fluid

L.P.A. Thai, Fanny Mousseau+3 more|arXiv (Cornell University)|Dec 12, 2019

Aerosol Filtration and Electrostatic PrecipitationEngineering68 references31 citations

TL;DR

This study investigates how engineered nanoparticles affect the bulk shear viscosity of a biomimetic lung surfactant using magnetic wire microrheology. It finds that cationic silica (42 nm) fluidifies the surfactant, while alumina (40 nm) induces a liquid-to-soft solid transition, with profound implications for surfactant reorganization during breathing.

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 time-lapse optical micros-copy. 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 proper-ties, even at low concentrations. In particular, we find that silica causes fluidification, while alumi-na induces a liquid-to-soft solid transition. Both phenomena are described quantitatively and ac-counted 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 breath-ing.

Motivation & Objective

• To investigate the effects of engineered nanoparticles on the bulk viscoelastic properties of pulmonary surfactant.
• To determine how nanoparticle-surfactant interactions alter fluid flow and structural dynamics in the alveolar hypophase.
• To assess the physiological relevance of these changes by relating nanoparticle concentrations to real-world exposure levels.
• To apply magnetic wire microrheology to measure viscosity and elasticity in small-volume, heterogeneous surfactant dispersions.

Proposed method

• Used magnetic rotational spectroscopy (MRS) with micron-sized magnetic wires actuated by rotating magnetic fields to probe local rheology.
• Prepared biomimetic Curosurf® at 44 g L⁻¹ lipid concentration and varied nanoparticle concentrations from 10⁻³ to 0.50 g L⁻¹.
• Employed time-lapse optical microscopy to track wire rotation and extract shear viscosity and elastic modulus.
• Calibrated the magnetic wires using water-glycerol mixtures with known viscosities (4.95–80.0 mPa·s) to determine the susceptibility anisotropy coefficient (Δχ = 0.054 ± 0.006).
• Conducted cryo-TEM and dynamic light scattering to confirm vesicle morphology and absence of aggregation.
• Correlated nanoparticle concentrations with alveolar exposure levels, estimating 24 µg to 240 µg of NPs per alveolar region.

Experimental results

Research questions

• RQ1 How do cationic silica and alumina nanoparticles alter the bulk shear viscosity of a biomimetic lung surfactant?
• RQ2 What is the mechanism behind the observed fluidification (silica) and gelation (alumina) transitions in the surfactant?
• RQ3 How do nanoparticle-surfactant interactions at low concentrations affect the surfactant’s ability to reorganize during the respiratory cycle?
• RQ4 To what extent do nanoparticle-induced viscosity changes correlate with real-world alveolar exposure levels?
• RQ5 Can magnetic wire microrheology accurately quantify viscosity and elasticity in complex, low-volume surfactant dispersions?

Key findings

• Cationic silica nanoparticles (42 nm) induce fluidification of the lung surfactant, reducing its bulk shear viscosity even at low concentrations (10⁻³ g L⁻¹).
• Alumina nanoparticles (40 nm) trigger a liquid-to-soft solid transition, significantly increasing the surfactant’s elasticity and viscosity, with a critical concentration threshold observed.
• The fluidification by silica and gelation by alumina are quantitatively described by colloidal physics models, indicating strong interfacial interactions with lipid vesicles.
• At a concentration of 10⁻² g L⁻¹, the nanoparticle exposure corresponds to ~240 µg of NPs in the entire alveolar region, equivalent to ~10,000 particles per alveolus.
• The Krieger-Dougherty equation accurately describes the viscosity dependence on vesicle volume fraction (𝜙), with a maximum packing fraction 𝜙* = 0.65.
• The study suggests that such viscosity and structural changes could impair the dynamic reorganization and recirculation of surfactant during breathing, potentially disrupting lung function.