Another limitation of MD simulation in the membrane study is the use of periodic boundary conditions, which makes it dificult to observe large-scale deformations and remodeling of membranes. To solve this problem, a strategy of combining multiscale methods is helpful. Therefore, in this study, we combined MD simulations and continuum mechanics calculations to investigate the physical properties and lateral pressure proiles of POPC/POPS membranes in the presence of Ca 2+ , as well as the resulting curvature and steady shapes of membranes. Our results showed that the mechanical properties of lipid bilayers, especially PS-rich bilayers, can be signiicantly inluenced by the presence of Ca 2+ , and asymmetrically distributed Ca 2+ ions lead to asymmetrical lateral stress in the two lealets of lipid bilayers. With this information adopted, continuum mechanics calculations showed that asymmetric stress can induce a negative curvature on membranes with respect to excessive Ca 2+ ions, and the resulting steady shape of vesicle membranes, either locally or globally spherical or multi-spherical, depends on the speciic Ca 2+ distribution around the membrane.