By integrating the advantages of lipids’ biocompatibility and nanobubbles’ potent physicochemical properties, lipid nanobubbles show a great potential in ultrasound molecular imaging and biocompatible drug/gene delivery. However, under the interactions of the ultrasound, lipid nanobubbles may fuse with the cell membrane, changing the local membrane component and re-distributing encapsulated gas molecules into the hydrophobic region of the cell membrane, which may greatly affect the dynamics of certain membrane proteins and thus functions of cells. Although molecular dynamics simulation provides a useful computational tool to reveal the related molecular mechanisms, the lack of coarse-grained gas model greatly restricts this purpose. In the current work, we developed a Martini-compatible coarse-grained gas model based on the results of previous experiments and atomistic simulations, which could be used for lipid nanobubble simulations with complicated lipid components. By comparing the results of well-designed lipid nanobubble, lipid bi-monolayer and lipid bilayer simulations, we further revealed the role of membrane curvature and interleaflet coupling in the liquid-liquid phase separation of lipid membranes. It is worth mention that our developed coarse-grained nitrogen gas model can also be used for other gas-water interface systems such as pulmonary surfactant, which may overcome the possible artefacts arising from the usage of vacuum for gas phase.