Pathological cardiolipin-promoted membrane hemifusion stiffens pulmonary surfactant membranes

Porras-Gómez, Marilyn; Shoaib, Tooba; Steer, Dylan; Espinosa‐Marzal, Rosa M.; Leal, Cecília

doi:10.1016/j.bpj.2022.02.018

Cited by 10 publications

(8 citation statements)

References 65 publications

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“…As essential components for mitochondrial and cellular functionality, disturbances in CL metabolism give rise to detrimental phenotypes. Additionally, increased CL would cause structural damage to pulmonary surfactant membranes . To the best of our knowledge, it was first discovered that 1-NP could regulate the abundance of CL.…”

Section: Resultsmentioning

confidence: 99%

Human Airway Organoids and Multimodal Imaging-Based Toxicity Evaluation of 1-Nitropyrene

Zhou,

Li,

Chen

et al. 2024

Environ. Sci. Technol.

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Despite significant advances in understanding the general health impacts of air pollution, the toxic effects of air pollution on cells in the human respiratory tract are still elusive. A robust, biologically relevant in vitro model for recapitulating the physiological response of the human airway is needed to obtain a thorough understanding of the molecular mechanisms of air pollutants. In this study, by using 1-nitropyrene (1-NP) as a proofof-concept, we demonstrate the effectiveness and reliability of evaluating environmental pollutants in physiologically active human airway organoids. Multimodal imaging tools, including live cell imaging, fluorescence microscopy, and MALDI-mass spectrometry imaging (MSI), were implemented to evaluate the cytotoxicity of 1-NP for airway organoids. In addition, lipidomic alterations upon 1-NP treatment were quantitatively analyzed by nontargeted lipidomics. 1-NP exposure was found to be associated with the overproduction of reactive oxygen species (ROS), and dysregulation of lipid pathways, including the SM-Cer conversion, as well as cardiolipin in our organoids. Compared with that of cell lines, a higher tolerance of 1-NP toxicity was observed in the human airway organoids, which might reflect a more physiologically relevant response in the native airway epithelium. Collectively, we have established a novel system for evaluating and investigating molecular mechanisms of environmental pollutants in the human airways via the combinatory use of human airway organoids, multimodal imaging analysis, and MS-based analyses.

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Section: Resultsmentioning

confidence: 99%

Human Airway Organoids and Multimodal Imaging-Based Toxicity Evaluation of 1-Nitropyrene

Zhou,

Li,

Chen

et al. 2024

Environ. Sci. Technol.

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“…Холестерин составляет примерно 4% ФЛ, что необходимо для поддержания структуры и свой ств липидного монослоя [10]. Кардиолипин является незначительным компонентом (менее 1,1%), но может играть важную роль в гомеостазе легких [11]. Эти липидные компоненты ЛС способствуют функциональности и стабильности альвеолярного эпителия и необходимы для поддержания газообмена O2 и CO2 [2].…”

Section: состав сурфактантаunclassified

The use of exogenous surfactant in pulmonological practice

Ignatova,

Antonov,

Zakharova

2024

Medicinskij sovet

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A lung surfactant is a complex mixture of lipids and proteins necessary to maintain proper lung function. Drug changes play an important role in chronic lung diseases such as chronic obstructive pulmonary disease, bronchial asthma and idiopathic pulmonary fibrosis. The purpose of this article is to substantiate the use of exogenous surfactant in various respiratory diseases, based on the analysis of publications in domestic and international medical journals, as well as their own experience of application in real clinical practice. This review primarily discusses the contribution of pulmonary surfactants to maintaining homeostasis of the respiratory system; optimal delivery routes; differences between natural and synthetic surfactant; diseases associated with impaired surfactant production, such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, acute respiratory distress syndrome, pulmonary alveolar proteinosis, cystic fibrosis. Special attention is paid to the immunological properties of specific proteins of surfactants A and D, their effect on protection against respiratory viral infection. Data on the direct effect of exogenous surfactant on pulmonary function, an increase in post-bronchodilation FEV1 and FVC are presented. Special attention is paid to the use of surfactant in the new coronavirus infection COVID-19. Pharmacological and therapeutic strategies to improve pulmonary surfactant dysfunction can prevent alveolar collapse, reduce the proinflammatory response, and limit viral infection. Currently, the use of surfactant preparations for the treatment of various respiratory diseases is being studied in several clinical trials, which will significantly revise the understanding of the therapeutic possibilities of an exogenous surfactant and expand its application areas.

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“…This includes lamellar vesicles ( L ), inverse hexagonal ( H II ) and bicontinuous cubic phases ( Q II ) [30][31][32][33][34][35][36][37][38][39][40]. The optimal mechanism to boost LNPs endosomal escape is to promote LNP-endosomal membrane fusion, a process that should take place in less than 30 seconds [41] and be independent from endosome acidification or the debated “proton sponge” effect [42][43]. The design of “fusogenic” LNPs has been exclusively attributed to tuning the molecular packing parameter of lipid molecules such that their spontaneous membrane curvature ( C 0 ) is negative [44][45].…”

Section: Mainmentioning

confidence: 99%

Lipid nanoparticle topology regulates endosomal escape and delivery of RNA to the cytoplasm

Zheng

Bandara

Leal

2022

Preprint

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RNA therapeutics have the potential to resolve a myriad of diseases caused by gene deficiency. Lipid nanoparticles (LNPs) are one of the most successful RNA delivery systems. However, expanding their application hinges on the discovery of next generation LNPs with high potency, cyto-specific targeting, and low side effects. Overcoming the difficulty of releasing cargo from endocytosed LNPs remains a significant hurdle. The endosomal escape of viral and non-viral nanoparticles relies on the topological transformation of membrane fusion pore formation followed by RNA translocation into the cytosol. In this study we show that LNP-RNA nanostructure modulates the energetic cost of LNP fusion with a target membrane. The inclusion of a new class of structurally-active lipids leads to superior LNP endosomal fusion, fast evasion of endosomal entrapment, and efficacious RNA delivery. Specifically, bicontinuous cubic RNA-LNPs, cuboplexes, have significantly higher endosomal escape rates and deliver more RNA compared to regular lamellar LNPs.

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Pathological cardiolipin-promoted membrane hemifusion stiffens pulmonary surfactant membranes

Cited by 10 publications

References 65 publications

Human Airway Organoids and Multimodal Imaging-Based Toxicity Evaluation of 1-Nitropyrene

Human Airway Organoids and Multimodal Imaging-Based Toxicity Evaluation of 1-Nitropyrene

The use of exogenous surfactant in pulmonological practice

Lipid nanoparticle topology regulates endosomal escape and delivery of RNA to the cytoplasm

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