Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F20%3A00535901" target="_blank" >RIV/61388963:_____/20:00535901 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.3389/fcell.2020.581016" target="_blank" >https://doi.org/10.3389/fcell.2020.581016</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fcell.2020.581016" target="_blank" >10.3389/fcell.2020.581016</a>

Result language

angličtina

Original language name

Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level

Original language 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10403 - Physical chemistry

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in cell and developmental biology

ISSN

2296-634X

e-ISSN

—

Volume of the periodical

8

Issue of the periodical within the volume

Nov 16

Country of publishing house

CH - SWITZERLAND

Number of pages

16

Pages from-to

581016

UT code for WoS article

000593914100001

EID of the result in the Scopus database

2-s2.0-85096902987