Ethylenediaminetetraacetic acid (EDTA) is frequently used in lipid experiments to remove redundant ions, such as Ca2+, from the sample solution. In this work, combining molecular dynamics (MD) simulations and Langmuir monolayer experiments, we show that on top of the expected Ca2+ depletion, EDTA anions themselves bind to phosphatidylcholine (PC) monolayers. This binding, originating from EDTA interaction with choline groups of PC lipids, leads to the adsorption of EDTA anions at the monolayer surface and concentration-dependent changes in surface pressure as measured by monolayer experiments and explained by MD simulations. This surprising observation emphasizes that lipid experiments carried out using EDTA-containing solutions, especially of high concentrations, must be interpreted very carefully due to potential interfering interactions of EDTA with lipids and other biomolecules involved in the experiment, e.g., cationic peptides, that may alter membrane-binding affinities of studied compounds.

• MeSH
• EDTA MeSH
• fosfatidylcholiny * chemie   MeSH
• ionty MeSH
• membrány umělé * MeSH
• simulace molekulární dynamiky MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• EDTA MeSH
• fosfatidylcholiny * MeSH
• ionty MeSH
• membrány umělé * MeSH

Lipid monolayers provide our lungs and eyes their functionality and serve as proxy systems in biomembrane research. Therefore, lipid monolayers have been studied intensively including using molecular dynamics simulations, which are able to probe their lateral structure and interactions with, e.g., pharmaceuticals or nanoparticles. However, such simulations have struggled in describing the forces at the air-water interface. Particularly, the surface tension of water and long-range van der Waals interactions have been considered critical, but their importance in monolayer simulations has been evaluated only separately. Here, we combine the recent C36/LJ-PME lipid force field that includes long-range van der Waals forces with water models that reproduce experimental surface tensions to elucidate the importance of these contributions in monolayer simulations. Our results suggest that a water model with correct surface tension is necessary to reproduce experimental surface pressure-area isotherms and monolayer phase behavior. The latter includes the liquid expanded and liquid condensed phases, their coexistence, and the opening of pores at the correct area per lipid upon expansion. Despite these improvements of the C36/LJ-PME with certain water models, the standard cutoff-based CHARMM36 lipid model with the 4-point OPC water model still provides the best agreement with experiments. Our results emphasize the importance of using high-quality water models in applications and parameter development in molecular dynamics simulations of biomolecules.

• MeSH
• lipidy MeSH
• povrchové napětí MeSH
• simulace molekulární dynamiky * MeSH
• voda * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lipidy MeSH
• voda * MeSH