Interactions of Novel Phosphonium Dye with Lipid Bilayers: A Molecular Dynamics Study

Abstract

In the present work the 100-ns molecular dynamics simulations (MD) were performed in the CHARMM36m force field using the GROMACS package to estimate the bilayer location and mechanisms of the interaction between the novel phosphonium dye TDV and the model lipid membranes composed of the phosphatidylcholine (PC) and its mixtures with cholesterol (Chol) or/and anionic phospholipid cardiolipin (CL). Varying the dye initial position relative to the membrane midplane, the dye relative orientation and the charge state of the TDV molecule it was found that the one charge form of TDV, which was initially translated to a distance of 20 Å from the membrane midplane along the bilayer normal, readily penetrates deeper into the membrane interior and remains within the lipid bilayer during the entire simulation time. It was revealed that the probe partitioning into the model membranes was accompanied by the reorientation of TDV molecule from perpendicular to nearly parallel to the membrane surface. The analysis of the MD simulation results showed that the lipid bilayer partitioning and location of the one charge form of TDV depend on the membrane composition. The dye binds more rapidly to the neat PC bilayer than to CL- and Chol-containing model membranes. It was found that in the neat PC and CL-containing membranes the one charge TDV resides at the level of carbonyl groups of lipids (the distances ~ 1.1 nm, 1.2 nm and 1.3 nm from the bilayer center for the PC, CL10 and CL20 lipid membranes, respectively), whereas in the Chol-containing membranes the probe is located at the level of glycerol moiety (~ 1.5 nm and 1.6 nm for the Chol30 and CL10/Chol30 lipid membranes, respectively). It was demonstrated that the dye partitioning into the lipid bilayer does not affect the membrane structural properties.