Location of the Hydrophobic Surfactant Proteins, SP-B and SP-C, in Fluid-Phase Bilayers

Loney, Ryan W.; Panzuela, S.; Chen, Jespar; Yang, Zimo; Fritz, Jonathan R.; Dell, Zachary; Corradi, Valentina; Kumar, Kamlesh; Tieleman, D. Peter; Hall, Stephen B.; Tristram-Nagle, Stephanie

doi:10.1021/acs.jpcb.0c03665

Cited by 12 publications

(29 citation statements)

References 69 publications

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“…Studies have yet to elucidate any direct interaction between vitamin E acetate and surfactant proteins; however, their common role in the stalk intermediate implies that they may be proximal . It has been established that changes in membrane physical properties can greatly influence and regulate protein function. − In fact, a number of previous studies demonstrate changes in the bending rigidity of pulmonary surfactant-like films as induced by small hydrophobic molecules. ,− Though we do not incorporate surfactant proteins in this work, we do study the lipids that comprise 90% of the PS.…”

Section: Discussionmentioning

confidence: 99%

A Mechanical Mechanism for Vitamin E Acetate in E-cigarette/Vaping-Associated Lung Injury

DiPasquale¹,

Gbadamosi²,

Nguyen³

et al. 2020

Chem. Res. Toxicol.

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The outbreak of electronic-cigarette/vaping-associated lung injury (EVALI) has made thousands ill. This lung injury has been attributed to a physical interaction between toxicants from the vaping solution and the pulmonary surfactant. In particular, studies have implicated vitamin E acetate as a potential instigator of EVALI. Pulmonary surfactant is vital to proper respiration through the mechanical processes of adsorption and interface stability to achieve and maintain low surface tension at the air−liquid interface. Using neutron spin echo spectroscopy, we investigate the impact of vitamin E acetate on the mechanical properties of two lipid-only pulmonary surfactant mimics: pure 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and a more comprehensive lipid mixture. It was found that increasing vitamin E acetate concentration nonlinearly increased membrane fluidity and area compressibility to a plateau. Softer membranes would promote adsorption to the air−liquid interface during inspiration as well as collapse from the interface during expiration. These findings indicate the potential for the failure of the pulmonary surfactant upon expiration, attributed to monolayer collapse. This collapse could contribute to the observed EVALI signs and symptoms, including shortness of breath and pneumonitis.

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Section: Discussionmentioning

confidence: 99%

A Mechanical Mechanism for Vitamin E Acetate in E-cigarette/Vaping-Associated Lung Injury

DiPasquale¹,

Gbadamosi²,

Nguyen³

et al. 2020

Chem. Res. Toxicol.

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“…The presence of proteins could influence the cholesterol adsorption to hydrophobic NPs as the interaction of lipids and peptides leads to lipoprotein formation in the surfactant layer. The interaction of PLs and surfactant protein has been the subject of previous experimental (in vivo and in vitro) − and simulation studies . An in vitro study has found that high-density lipoprotein (transferable/mimicable to natural high-density lipoprotein in cells) regulates the properties of cholesterol binding to the AuNPs.…”

Section: Introductionmentioning

confidence: 99%

Computational Studies of Lipid-Wrapped Gold Nanoparticle Transport Through Model Lung Surfactant Monolayers

et al. 2021

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Colloidal nanoparticles, such as gold nanoparticles (AuNPs), are promising materials for the delivery of hydrophilic drugs via the pulmonary route. The inhaled nanoparticle drug carriers primarily deposit in lung alveoli and interact with the alveolar surface known as lung surfactants. Therefore, it is vital to understand the interactions of nanocarriers with the surfactant layer. To understand the interactions at the molecular level, here we simulated model lung surfactant monolayers with phospholipid (PL)-wrapped AuNPs at the vacuum–water interface using coarse-grained molecular dynamics simulations. The PL-wrapped AuNPs quickly adsorbed into the surfactant layer, altered the structural properties of the monolayer, and at high concentrations initiated the compressed monolayer to collapse/buckle. Among the surfactant monolayer lipid components, cholesterol adsorbed to the AuNPs preferentially over PL species. The position of the adsorbed PL-AuNPs within the monolayer, and subsequent monolayer perturbation, vary depending on the monolayer phase, monolayer composition, and species of PL used as a ligand. Information provided by these molecular dynamic simulations helps to rationalize why some colloidal nanoparticles work better as nanocarriers than others and aid the design of new ones, to avoid biological toxicity and improve efficacy for pulmonary drug delivery.

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“…Studies on lipid membranes have revealed that the inclusion of SP-B has little effect on the acyl chain region, 37,38 yet it affects the thermodynamic behavior of membranes. 39 These findings, together with X-ray diffuse scattering (XDS) results, 40 place SP-B in the head group region in lipid bilayers. XDS experiments 40 also detect protein density at the membrane core, which is associated with SP-C and agrees with its parallel orientation along the membrane plane.…”

Section: Introductionmentioning

confidence: 91%

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

Liekkinen

Olżyńska

Ćwiklik

et al. 2022

Preprint

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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 byz-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.

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Location of the Hydrophobic Surfactant Proteins, SP-B and SP-C, in Fluid-Phase Bilayers

Cited by 12 publications

References 69 publications

A Mechanical Mechanism for Vitamin E Acetate in E-cigarette/Vaping-Associated Lung Injury

A Mechanical Mechanism for Vitamin E Acetate in E-cigarette/Vaping-Associated Lung Injury

Computational Studies of Lipid-Wrapped Gold Nanoparticle Transport Through Model Lung Surfactant Monolayers

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

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