Coarse-grained (CG) MD simulations were conducted to explore the effect of ethanol (concentration) on the POPC bilayer (lamellar) structure. First, a lamellar structure containing three POPC bilayers is constructed in the simulation box with water at a proper hydration level to explain the d-spacing of 6.1 nm (System 1). We calculate the structure factor using the MD trajectory to confirm the consistency of the simulation results with those obtained experimentally (Figure ). We then replace several randomly selected water (WAT) particles with ethanol (ETNL) particles to explore a possible structural change due to the increment of ethanol concentration, which is detected as a d-spacing variation (see Figure for the definitions of the CG particles). Here, we assume that one WAT particle, which represents three water molecules, is replaced by one ETNL particle, which represents a single ethanol molecule. With increasing ethanol concentration, the POPC bilayer expands laterally, reducing the membrane thickness. Thus, we may obtain reasonable POPC bilayer models (Systems 2 and 3) to explain the respective dspacings of 4.7 and 4.4 nm, as observed using SAXS. The lamellar structures obtained at ethanol concentrations of 48 and 57 vol.% reasonably explain the structure factors obtained via SAXS (Figures and). We conducted a 1 µs MD simulation for each system, and the snapshot obtained for each system is shown in Figure . The molecular areas (cross-sectional area per lipid molecule) and dPP (phosphate-phosphate distance along the bilayer normal, representing membrane thickness) averaged over the MD trajectories of Systems 1-3 are shown in Table . With increasing ethanol concentration, the molecular area is significantly increased by 30% (System 2) and 40% (System 3), whereas dPP is decreased by 11% (System 2) and 13% (System 3). Thus, the effective volume of the membrane is increased by increasing the ethanol concentration, because the POPC bilayer membrane is swollen with ethanol. Figure shows the number density profiles of selected CG segments along the bilayer normals.