Liekkinen, J. | bioRxiv Science

bioRxiv2023

Exposure to aldehyde cherry e-liquid flavouring and its vape by-product disrupts pulmonary surfactant biophysical function

Over the last decade there has been a surge in vaping device usage, especially among adolescents, raising concerns for potentially related lung damage. Notoriously, there have been many e-cigarette or vaping-related lung injury (EVALI) cases resulting in hospitalisations and deaths. Although the vaping component vitamin E acetate has been linked to a large proportion of EVALI cases resulting in its widespread banning, one fifth of the cases remain unexplained. Furthermore, the overall long-term impact of vaping on respiratory health is poorly understood. A likely driver behind EVALI is pulmonary surfactant disruption, as it is the first point of contact for any inhaled toxicant in the alveoli, and abnormalities of its function are linked to some symptoms presented in EVALI cases. Aberrant biophysical function of the surfactant results in alveolar surface tension increase, causing alveolar collapse. Vaping chemicals with the potential to disrupt surfactant function must be hydrophobic molecules able to interact with surfactant components at the alveolar air-liquid interface. Recent findings have recorded the synthesis of highly hydrophobic acetal by-products of the base vaping chemical propylene glycol and common flavouring aldehydes, including the cherry flavouring benzaldehyde, not identified in preliminary e-liquid safety tests. This study provides evidence that benzaldehyde and its by-product, benzaldehyde propylene glycol acetal, have the potential to significantly disrupt surfactant biophysical function via interactions with surfactant proteins SP-B and/or SP-C, which may provide stable interactions within the surfactant film by forming associations with the sublayer of surfactant three-dimensional structure present at high lateral compression, i.e., expiration breathing. Data also suggest considerable vaping chemical loss to the experimental subphase, indicating potential further implications to the alveolar epithelial layer beneath.

pharmacology and toxicology↗

bioRxiv2022

Surfactant Proteins SP-B and SP-C in Pulmonary Surfactant Monolayers: Physical Properties Controlled by Specific Protein-Lipid Interactions

The lining of the alveoli is covered by pulmonary surfactant, a complex mixture of surface-active lipids and proteins that enables efficient gas exchange between inhaled air and the circulation. Despite decades of advancements in the study of the pulmonary surfactant, the molecular scale behavior of the surfactant and the inherent role of the number of different lipids and proteins in surfactant behavior are not fully understood. The most important proteins in this complex system are the surfactant proteins SP-B and SP-C. Given this, in this work we performed non-equilibrium all-atom molecular dynamics simulations to study the interplay of SP-B and SP-C with multi-component lipid monolayers mimicking the pulmonary surfactant in composition. The simulations were complemented by z-scan fluorescence correlation spectroscopy and atomic force microscopy measurements. Our state-of-the-art simulation model reproduces experimental pressure-area isotherms and lateral diffusion coefficients. In agreement with previous research, the inclusion of either SP-B and SP-C increases surface pressure, and our simulations provide a molecular scale explanation for this effect: The proteins display preferential lipid interactions with phosphatidylglycerol, they reside predominantly in the lipid acyl chain region, and they partition into the liquid expanded phase or even induce it in an otherwise packed monolayer. The latter effect is also visible in our atomic force microscopy images. The research done contributes to a better understanding of the roles of specific lipids and proteins in surfactant function, thus helping to develop better synthetic products for surfactant replacement therapy used in the treatment of many fatal lung-related injuries and diseases.

biophysics↗