Coarse-grained molecular dynamics simulations of phase transitions in mixed lipid systems containing LPA, DOPA, and DOPE lipids

The mechanisms that mediate biomembrane shape transformations are of considerable interest in cell biology. Recent in vitro experiments show that the chemical transformation of minor membrane lipids can induce dramatic shape changes in biomembranes. Specifically, it was observed that the addition of DOPA to DOPE has no effect on the stability of the bilayer structure of the membrane. In contrast, the addition of LPA to DOPE stabilizes the bilayer phase of DOPE, increasing the temperature of a phase transition from the bilayer to the inverted hexagonal phase. This result suggests that the chemical conversion of DOPA to LPA is sufficient for triggering a dramatic change in the shape of biomembranes. The LPA/DOPA/DOPE mixture of lipids provides a simple model system for understanding the molecular events driving the shape change. In this work, we used coarse-grained molecular dynamics simulations to study the phase transitions of this lipid mixture. We show that despite the simplicity of the coarse-grained model, it reproduces the experimentally observed phase changes of: 1), pure LPA and DOPA with respect to changes in the concentration of cations; and 2), LPA/DOPE and DOPA/DOPE mixtures with respect to temperature. The good agreement between the model and experiments suggests that the computationally inexpensive coarse-grained approach can be used to infer macroscopic membrane properties. Furthermore, analysis of the shape of the lipid molecules demonstrates that the phase behavior of single-lipid systems is consistent with molecular packing theory. However, the phase stability of mixed lipid systems exhibits significant deviations from this theory, which suggests that the elastic energy of the lipids, neglected in the packing theory, plays an important role.