The plasma membrane serves as a crucial protective barrier for the cell, composed of two monolayers of lipids that assemble to form a cohesive bilayer. Interestingly, the lipid structures in one monolayer differ from those in the other, as if the composition of each is cleverly selected to face the internal and external challenges posed by both environments surrounding the membrane. With the advancement of new experimental methods to engineer asymmetric lipid bilayers under laboratory conditions, experimental results have highlighted a powerful influence of one monolayer on another. Here, we prepare asymmetric giant unilamellar vesicles using the hemifusion method. In our model of the exoplasmic monolayer, the lipid composition forms liquid disordered and liquid ordered phases, whereas the model of the cytosolic monolayer comprises unsaturated lipids and cholesterol to mimic a highly fluid environment. We selected a set of results to show that, depending on the lipid composition, the phase-separated leaflet can induce ordered domains within the highly fluid leaflet. In this case, the induced ordered domains became enriched in cholesterol. However, decreasing the length of the saturated lipid in the phase-separated leaflet results in domains no longer being observed under the microscope. Why are induced order domains not always observed? A competition between intra- and inter-leaflet interactions can explain both results, thereby resolving this apparent paradox. In both cases, the inter-leaflet interaction plays a role in how one leaflet affects the other and controls the bilayer phase behavior. Interestingly, an experimental condition where one leaflet has little influence on the other has yet to be found.
Thais A. Enoki (Sun,) studied this question.