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Biophysical insults that either reduce barrier function (COVID-19, smoke inhalation, aspiration, and inflammation) or increase mechanical stress (surfactant dysfunction) make the lung more susceptible to atelectrauma. We investigate the susceptibility and time-dependent disruption of barrier function associated with pulmonary atelectrauma of epithelial cells that occurs in acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). This in vitro study was performed using Electric Cell-substrate Impedance Sensing (ECIS) as a noninvasive evaluating technique for repetitive stress stimulus/response on monolayers of the human lung epithelial cell line NCI-H441. Atelectrauma was mimicked through recruitment/derecruitment (RD) of a semi-infinite air bubble to the fluid-occluded micro-channel. We show that a confluent monolayer with a high level of barrier function is nearly impervious to atelectrauma for hundreds of RD events. Nevertheless, barrier function is eventually diminished, and after a critical number of RD insults, the monolayer disintegrates exponentially. Confluent layers with lower initial barrier function are less resilient. These results indicate that the first line of defense from atelectrauma resides with intercellular binding. After disruption, the epithelial layer community protection is diminished and atelectrauma ensues. ECIS may provide a platform for identifying damaging stimuli, ventilation scenarios, or pharmaceuticals that can reduce susceptibility or enhance barrier-function recovery.
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Opto-electromechanical quantification of epithelial barrier function in injured and healthy airway tissues
The airway epithelium lining the luminal surface of the respiratory tract creates a protective barrier that ensures maintenance of tissue homeostasis and prevention of respiratory diseases. The airway epithelium, unfortunately, is frequently injured by inhaled toxic materials, trauma, or medical procedures. Substantial or repeated airway epithelial injury can lead to dysregulated intrinsic repair pathways and aberrant tissue remodeling that can lead to dysfunctional airway epithelium. While disruption in the epithelial integrity is directly linked to degraded epithelial barrier function, the correlation between the structure and function of the airway epithelium remains elusive. In this study, we quantified the impact of acutely induced airway epithelium injury on disruption of the epithelial barrier functions. By monitoring alternation of the flow motions and tissue bioimpedance at local injury site, degradation of the epithelial functions, including mucociliary clearance and tight/adherens junction formation, were accurately determined with a high spatiotemporal resolution. Computational models that can simulate and predict the disruption of the mucociliary flow and airway tissue bioimpedance have been generated to assist interpretation of the experimental results. Collectively, findings of this study advance our knowledge of the structure–function relationships of the airway epithelium that can promote development of efficient and accurate diagnosis of airway tissue injury.
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- Award ID(s):
- 2143620
- PAR ID:
- 10584165
- Publisher / Repository:
- American Institute of Physics
- Date Published:
- Journal Name:
- APL Bioengineering
- Volume:
- 7
- Issue:
- 1
- ISSN:
- 2473-2877
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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