ECM (fibronectin or collagen)
ECM refers to Extracellular Matrix, connective tissues used for (but not limited to) anchoring cells. Here, the authors used Fibronectin ( that helps connect cells to the ECM) and Collagen (that is the main structural proteins in connective tissue) to help culture cells on both sides of the thin polymeric membrane.
Our results clearly show that the epithelial cells not only remained viable but also increased their surfactant production, enhanced their structural integrity, and restored normal barrier permeability in this biomimetic microsystem.
This is confirming that the device's epithelial layer of cells was able to survive, create surfactants, become more structurally stable, and be selectively permeable much like those epithelial cells of the alveolar-capillary interfaces found in the human lung.
neutrophils
The most common type of white blood cell in humans (40-70%), whose function varies between animal to animal. In humans they are the first responders to combat the intruder while signaling to other immune cells for more help.
quantum dots
Nanoscopic fluorescent particles used to track and quantify membrane stretching
only exhibited low levels of nanoparticle translocation (Fig. 4G).
Transwell culture involves growing cells on a porous membrane to mimic the physiological environment of certain tissues and organs; the study found that static Transwell systems had fewer nanoparticles moving across the cell barrier, while the lung mimicking microdevice showed a larger number of nanoparticles crossing the barrier.
we found that nanoparticle transport from the alveoli into the microvasculature was significantly increased in the presence of cyclic breathing in vivo (Fig. 4I), just as we observed in the lung mimic device in vitro (Fig. 4G).
This is showing that the in vivo mouse model dosed with nanoparticles showed a higher number of nanoparticles moving across the alveolar-capillary interface, which is similar to the results obtained from the lung mimic device.
The level was similar to that measured with a static Transwell culture system containing a rigid, porous, ECM-coated membrane lined with opposing layers of alveolar epithelium and capillary endothelium (Fig. 4G). In contrast, there was an increase by more than a factor of 4 in nanoparticle transport into the vascular compartment when our microdevice experienced physiological breathing motions (10% strain at 0.2 Hz) (Fig. 4G). This was striking given that transport of fluorescent albumin remained unchanged under similar loading conditions (fig. S1). Thus, strain-induced increases in nanoparticle absorption across the alveolar-capillary barrier are not due to physical disruption of cell-cell junctions and simple convective transport. Instead, they more likely result from altered transcellular translocation or from a change in paracellular transport that somehow selectively permits passage of these nanoparticulates while restricting movement of small molecules, such as albumin.
These results state that physiological breathing motions caused an increase in nanoparticle transport across the alveolar-capillary barrier, which was not due to physical disruption of cell-cell junctions. The mechanism behind this phenomenon may help us gain a better understanding of how these nanoparticles translocate across tissues and cause toxicity.
Indeed, this mechanical strain–induced oxidative response appeared to be specific for the silica nanoparticles and carboxylated quantum dots, because it was not induced by treatment with various other nanomaterials, including single-walled carbon nanotubes, gold nanoparticles, polystyrene nanoparticles, or polyethylene glycol–coated quantum dots (fig. S8 and table S1). On the other hand, we found that longer exposure to silica nanoparticles alone for 24 hours induced similar high levels of ROS production even in the absence of mechanical strain (fig. S7), confirming findings of past pulmonary nanotoxicology studies that analyzed the effects of ultrafine silica nanoparticles in static cell cultures (34). Taken together, these data suggest that physiological mechanical stresses due to breathing might act in synergy with nanoparticles to exert early toxic effects or accelerate nanoparticle toxicity in the lung.
The findings indicated that although introducing simulated mechanical strain had no additional toxic effect for certain nanoparticles, others (specifically, silica nanoparticles and carboxylated quantum dots) demonstrated toxicity, especially at the early stages of exposure.
inspiration
drawing in breath/ breathing in
However, our results extend this observation by providing evidence to suggest that breathing motions might greatly accentuate the proinflammatory activities of silica nanoparticles and contribute substantially to the development of acute lung inflammation.
This is describing that the inflammatory response due to silica nanoparticles was significantly greater when strain simulating breathing was applied, meaning that the device can simulate the effects of nanoparticles much more accurately than any stagnant cell culture ever could.
These results show that this bioinspired microdevice can effectively recapitulate the normal integrated cellular immune response to microbial infection in human lung alveoli
Here the researchers are testing whether their microdevice can simulate the alveolar-capillary interface, by triggering a proper immune response to an infection. They observed that when they exposed the alveolar side to a bacterial pathogen (E. coli), neutrophils on the capillary side migrated across the membrane to render them ineffective. A similar immune response is observed in the human body, confirming that the microdevice emulates lung physiology properly.
unidirectional mechanical strain
Deformation of a body caused by an outside force in one direction.
phagocytosis
The process where a cell engulfs a smaller particle (bacteria, smaller cells, etc) where it is trapped and subsequently defused.
intrapleural pressure
Pressure associated within the pleural cavity, the space enclosed by the pleura, which is a thin layer of tissue that covers the lungs and lines the interior wall of the chest cavity.
nanotoxicology
the study of adverse health effects of nanoscale (with sizes on the order of 10^-9 meters) particles.
alveolar-capillary interface
where exchange of gasses such as oxygen and carbon dioxide occurs between the tiny air sacs in lung (alveolus) and capillaries.
physiological
Refers to the physical actions of normal bodily processes.
The permeability of the alveolar-capillary barrier to fluorescent albumin remained unchanged during cyclic stretching over 4 hours with physiological levels of strain (5 to ~15%) or after preconditioning with 10% strain for varying amounts of time (fig. S1).
This is confirming that there is no leakage of albumin, a globular protein found in serum, between the alveolar lung side of the chip and the capillary side during the chip's physiological simulation of breathing.
peristalsis
Involuntary contraction or relaxation in a muscular canal (such as intestines) causing wave-like movements.