Ions at the two sides of the plasma membrane maintain the transmembrane potential, participate in signaling, and affect the properties of the membrane itself. The extracellular leaflet is particularly enriched in phosphatidylcholine lipids and under the influence of Na+, Ca2+, and Cl- ions. In this work, we combined molecular dynamics simulations performed using state-of-the-art models with vibrational sum frequency generation (VSFG) spectroscopy to study the effects of these key ions on the structure of dipalmitoylphosphatidylcholine. We used lipid monolayers as a proxy for membranes, as this approach enabled a direct comparison between simulation and experiment. We find that the effects of Na+ are minor. Ca2+, on the other hand, strongly affects the lipid headgroup conformations and induces a tighter packing of lipids, thus promoting the liquid condensed phase. It does so by binding to both the phosphate and carbonyl oxygens via direct and water-mediated binding modes, the ratios of which depend on the monolayer packing. Clustering analysis performed on simulation data revealed that changes in area per lipid or CaCl2 concentration both affect the headgroup conformations, yet their effects are anticorrelated. Cations at the monolayer surface also attract Cl-, which at large CaCl2 concentrations penetrates deep to the monolayer. This phenomenon coincides with a radical change in the VSFG spectra of the phosphate group, thus indicating the emergence of a new binding mode.

Department of Chemistry and Biochemistry The Ohio State University Columbus Ohio 43210 United States

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo nám 542 2 160 00 Prague 6 Czech Republic

J Heyrovsky Institute of Physical Chemistry of the Czech Academy of Sciences Dolejskova 3 18223 Prague 8 Czech Republic

Citace poskytuje Crossref.org

Stealthy Player in Lipid Experiments? EDTA Binding to Phosphatidylcholine Membranes Probed by Simulations and Monolayer Experiments

Accurate Simulations of Lipid Monolayers Require a Water Model with Correct Surface Tension