Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level
Pulmonary surfactant is a complex mixture of lipids and proteins lining the interior of the alveoli, and constitutes the first barrier to both oxygen and pathogens as they progress toward blood circulation. Despite decades of study, the behavior of the pulmonary surfactant at the molecular scale is...
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| Format: | Article |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.581016/full |
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| author | Juho Liekkinen Berta de Santos Moreno Riku O. Paananen Ilpo Vattulainen Ilpo Vattulainen Ilpo Vattulainen Luca Monticelli Jorge Bernardino de la Serna Matti Javanainen Matti Javanainen |
| author_facet | Juho Liekkinen Berta de Santos Moreno Riku O. Paananen Ilpo Vattulainen Ilpo Vattulainen Ilpo Vattulainen Luca Monticelli Jorge Bernardino de la Serna Matti Javanainen Matti Javanainen |
| author_sort | Juho Liekkinen |
| collection | DOAJ |
| description | Pulmonary surfactant is a complex mixture of lipids and proteins lining the interior of the alveoli, and constitutes the first barrier to both oxygen and pathogens as they progress toward blood circulation. Despite decades of study, the behavior of the pulmonary surfactant at the molecular scale is poorly understood, which hinders the development of effective surfactant replacement therapies, useful in the treatment of several lung-related diseases. In this work, we combined all-atom molecular dynamics simulations, Langmuir trough measurements, and AFM imaging to study synthetic four-component lipid monolayers designed to model protein-free pulmonary surfactant. We characterized the structural and dynamic properties of the monolayers with a special focus on lateral heterogeneity. Remarkably, simulations reproduce almost quantitatively the experimental data on pressure-area isotherms and the presence of lateral heterogeneities highlighted by AFM. Quite surprisingly, the pressure-area isotherms do not show a plateau region, despite the presence of liquid-condensed nanometer-sized domains at surface pressures larger than 20 mN/m. In the simulations, the liquid-condensed domains were small and transient, but they did not coalesce to yield a separate phase. They were only slightly enriched in DPPC and cholesterol, and their chemical composition remained very similar to the overall composition of the monolayer membrane. Instead, they differed from liquid-expanded regions in terms of membrane thickness (in agreement with AFM data), diffusion rates, as well as acyl chain packing and orientation. We hypothesize that such lateral heterogeneities are crucial for lung surfactant function, as they allow both efficient packing, to achieve low surface tension, and sufficient fluidity, critical for rapid adsorption to the air–liquid interface during the breathing cycle. |
| first_indexed | 2024-12-14T08:20:43Z |
| format | Article |
| id | doaj.art-8209e5ab9d3145aeb1c247cd64701baf |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-14T08:20:43Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-8209e5ab9d3145aeb1c247cd64701baf2022-12-21T23:09:49ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-11-01810.3389/fcell.2020.581016581016Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic LevelJuho Liekkinen0Berta de Santos Moreno1Riku O. Paananen2Ilpo Vattulainen3Ilpo Vattulainen4Ilpo Vattulainen5Luca Monticelli6Jorge Bernardino de la Serna7Matti Javanainen8Matti Javanainen9Department of Physics, University of Helsinki, Helsinki, FinlandNational Heart & Lung Institute, Faculty of Medicine, Imperial College London, London, United KingdomHelsinki Eye Lab, Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandDepartment of Physics, University of Helsinki, Helsinki, FinlandComputational Physics Laboratory, Tampere University, Tampere, FinlandMEMPHYS – Centre for Biomembrane Physics, Odense, DenmarkMolecular Microbiology and Structural Biochemistry (MMSB), UMR 5086 CNRS & University of Lyon, Lyon, FranceNational Heart & Lung Institute, Faculty of Medicine, Imperial College London, London, United KingdomComputational Physics Laboratory, Tampere University, Tampere, FinlandInstitute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, CzechiaPulmonary surfactant is a complex mixture of lipids and proteins lining the interior of the alveoli, and constitutes the first barrier to both oxygen and pathogens as they progress toward blood circulation. Despite decades of study, the behavior of the pulmonary surfactant at the molecular scale is poorly understood, which hinders the development of effective surfactant replacement therapies, useful in the treatment of several lung-related diseases. In this work, we combined all-atom molecular dynamics simulations, Langmuir trough measurements, and AFM imaging to study synthetic four-component lipid monolayers designed to model protein-free pulmonary surfactant. We characterized the structural and dynamic properties of the monolayers with a special focus on lateral heterogeneity. Remarkably, simulations reproduce almost quantitatively the experimental data on pressure-area isotherms and the presence of lateral heterogeneities highlighted by AFM. Quite surprisingly, the pressure-area isotherms do not show a plateau region, despite the presence of liquid-condensed nanometer-sized domains at surface pressures larger than 20 mN/m. In the simulations, the liquid-condensed domains were small and transient, but they did not coalesce to yield a separate phase. They were only slightly enriched in DPPC and cholesterol, and their chemical composition remained very similar to the overall composition of the monolayer membrane. Instead, they differed from liquid-expanded regions in terms of membrane thickness (in agreement with AFM data), diffusion rates, as well as acyl chain packing and orientation. We hypothesize that such lateral heterogeneities are crucial for lung surfactant function, as they allow both efficient packing, to achieve low surface tension, and sufficient fluidity, critical for rapid adsorption to the air–liquid interface during the breathing cycle.https://www.frontiersin.org/articles/10.3389/fcell.2020.581016/fullpulmonary surfactantlipid monolayermolecular dynamics simulationpressure-area isothermatomic force microscopyheterogeneity |
| spellingShingle | Juho Liekkinen Berta de Santos Moreno Riku O. Paananen Ilpo Vattulainen Ilpo Vattulainen Ilpo Vattulainen Luca Monticelli Jorge Bernardino de la Serna Matti Javanainen Matti Javanainen Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level Frontiers in Cell and Developmental Biology pulmonary surfactant lipid monolayer molecular dynamics simulation pressure-area isotherm atomic force microscopy heterogeneity |
| title | Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level |
| title_full | Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level |
| title_fullStr | Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level |
| title_full_unstemmed | Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level |
| title_short | Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level |
| title_sort | understanding the functional properties of lipid heterogeneity in pulmonary surfactant monolayers at the atomistic level |
| topic | pulmonary surfactant lipid monolayer molecular dynamics simulation pressure-area isotherm atomic force microscopy heterogeneity |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2020.581016/full |
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