Monte Carlo simulations of the distributions of intra- and extra-vesicular ions and membrane associated charges in hybrid liposomes composed of negatively charged tetraether and zwitterionic diester phospholipids

Abstract

Here, we model a negatively charged lipid vesicle, composed of a mixture of bipolar tetraether and diester (or diether) phospholipid molecules, by a spherical shell that has zero ion permeability. We take into consideration all the charge-charge interactions between intra-vesicular ions, extra-vesicular ions, and membrane lipid associated charges. Monte Carlo simulations result in homogeneous and double-exponential ion distribution, respectively, in the intra- and extra-vesicular space. The extra-vesicular ion concentration close to the membrane surface is proportional to the total amount of the membrane charges (Nm) and is independent of the partitioning of the membrane charges between the outer (Nom) and inner membrane (Nim) surface. This result shows that one should not disregard the effect of the charges on the inner membrane surface when calculating the ion distributions around a charged vesicle. If the partitioning of the membrane charges is not restricted (i.e., lipid flip-flop is allowed), then at different Nm, the Nom/Nim ratio remains constant and the value of Nom/Nim, as a consequence of the interaction between every charges of the model, is close to, but significantly higher than, the ratio of the outer to the inner surface area of the membrane. These results indicate that the amount and the orientation of the negatively-charged tetraether lipids in the membrane are important determinants of membrane properties in tetraether/zwitterionic diester phospholipid liposomes. Finally we compared the results of our discrete charge model and continuous models based on the solutions of the Poisson-Boltzmann equation and pointed out qualitative similarities and sometimes major quantitative differences between these two types of models.