Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level.
atomic force microscopy
heterogeneity
lipid monolayer
membrane domain
molecular dynamics simulation
pressure-area isotherm
pulmonary surfactant
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2020
2020
Historique:
received:
07
07
2020
accepted:
16
10
2020
entrez:
11
12
2020
pubmed:
12
12
2020
medline:
12
12
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33304898
doi: 10.3389/fcell.2020.581016
pmc: PMC7701215
doi:
Banques de données
figshare
['10.6084/m9.figshare.12612317']
Types de publication
Journal Article
Langues
eng
Pagination
581016Informations de copyright
Copyright © 2020 Liekkinen, de Santos Moreno, Paananen, Vattulainen, Monticelli, Bernardino de la Serna and Javanainen.
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