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Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level
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SYSNO ASEP 0535901 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level Author(s) Liekkinen, J. (FI)
de Santos Moreno, B. (GB)
Paananen, R. O. (FI)
Vattulainen, I. (FI)
Monticelli, L. (FR)
de la Serna, J. B. (GB)
Javanainen, Matti (UOCHB-X) RID, ORCIDArticle number 581016 Source Title Frontiers in Cell and Developmental Biology. - : Frontiers Research Foundation - ISSN 2296-634X
Roč. 8, Nov 16 (2020)Number of pages 16 s. Language eng - English Country CH - Switzerland Keywords pulmonary surfactant ; lipid monolayer ; molecular dynamics simulation ; pressure-area isotherm ; atomic force microscopy ; heterogeneity ; membrane domain Subject RIV CF - Physical ; Theoretical Chemistry OECD category Physical chemistry Method of publishing Open access Institutional support UOCHB-X - RVO:61388963 UT WOS 000593914100001 EID SCOPUS 85096902987 DOI 10.3389/fcell.2020.581016 Annotation 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. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2021 Electronic address https://doi.org/10.3389/fcell.2020.581016
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