Asymmetrical calcium ions induced stress and remodeling in lipid bilayer membranes

Ca2+ ions play crucial roles in regulating many chemical and biological processes, but their impact on lipid bilayer membranes remains elusive, especially when the impacts on the two leaflets are asymmetrical. Using a recently developed multisite Ca2+ model, we performed molecular dynamics simulations to study the impact of Ca2+ on the properties of membranes composed of POPC and POPS and observed that both the structure and fluidity of the membranes were significantly affected. In particular, we examined the influence of asymmetrically distributed Ca2+ on asymmetric lipid bilayers and found that imbalanced stress in the two leaflets was generated, with the negatively charged leaflet on the Ca2+-rich side becoming more condensed, which in turn induced membrane curvature that bent the membrane away from the Ca2+-rich side. We employed continuum mechanics to study the large-scale deformations of a spherical vesicle and found that the vesicle can go through vesiculation to form a multi-spherical shape in which a number of spheres are connected with infinitesimal necks, depending on the specific Ca2+ distributions. These results provide new insights into the underlying mechanisms of many biological phenomena involving Ca2+-membrane interactions and may lead to new methods for manipulating the membrane curvature of vesicles in chemical, biological, and nanosystems.