Probing the Ripple Phase of Lipid Bilayers using Molecular Simulations

Abstract

Lipid bilayers without sterols can exist in the gel, ripple, and liquid-crystalline phase depending on temperature. The ripple phase is the mysterious transition phase between gel and liquid-crystalline phases. For this work, a set of molecular dynamics (MD) simulations were carried out for pure 1,2-dimyristoyl-3-sn-phosphatidylcholines (DMPC), pure 1,2-dipalmitoyl-3-sn-phosphatidylcholine (DPPC), and their mixture at different temperatures. For some mixture and pure DMPC conditions, simulations were also performed in larger system size (144 lipids for each leaflet), which was four times bigger than small system (36 lipids for each leaflet), to determine its influence on ripple phase structure. Simulations were performed for 300ns, and the CHARMM 36 force field was used (J. Phys. Chem. B., 114, 7830-7843). For pure DMPC and DPCC (small system), ripple phase was obtained at 275 and 293K, respectively. For small system size of the DMPC-DPPC mixture, which had %75 DMPC, the ripple phase was obtained at slightly higher temperature at 298K. Ripple conformations were fairly stable at the last 100 ns of simulations. Interestingly, for large system of pure DMPC simulation, ripple phase was obtained at 291K, which is the temperature that ripple phase was observed based on X-ray scattering technique (Soft Matter, 11, 918-926). In case of DMPC-DPPC mixture with large system size, ripple phase was still obtained in a fairly stable conformation. Moreover, in large system set up for both pure DMPC and DMPC-DPPC mixture, the ripple length was increased, which is more in agreement with experiment. Form factor from simulations will be compared with 2D X-ray form factors from experiment (Soft Matter, 11, 918-926). In overall, CHARMM 36 force field can predict the ripple phase within reasonable range of temperatures and provide interpretation of experimental form factors.