Therefore, when the stiffness κ of the monolayer film is large ( 𝜅 > 10 𝑘 𝑇 ), the minimized bending free energy 𝐹 will drive the equilibrium size of the nanobubble approaching 𝑅 since 𝜅̅ is a relatively small in magnitude. In other words, for stiff monolayers it is the spontaneous curvature 𝑐 = 1/𝑅 that determines the size of bulk nanobubbles. 𝑐 or 𝑅 can be directly related to the shape of amphiphilic molecules, indicating the tendency of the interface to curve toward either the water (𝑐 > 0) or the gas (𝑐 < 0). As shown in our molecular dynamic simulations, 𝑐 < 0 is required for stable nanobubbles.