Spontaneously formed monodisperse biomimetic unilamellar vesicles: the effect of charge, dilution, and time

Using small-angle neutron scattering and dynamic light scattering, we have constructed partial structural phase diagrams of lipid mixtures composed of the phosphatidylcholines dimyristoyl and dihexanoyl doped with calcium ions (Ca2+) and/or the negatively charged lipid, dimyristoyl phosphatidylglycerol (DMPG). For dilute solutions (lipid concentration ≤1wt%), spontaneously forming unilamellar vesicles (ULVs) were found, and their polydispersity was determined to be ∼20%. The stability of the Ca2+- or DMPG-doped ULVs was monitored over a period of 4 days and their structural parameters (e.g., average outer radius, <Ro>) were found to be insensitive to the lipid concentration (Clp). However, doping the dimyristoyl/dihexanoyl system with both Ca2+ and DMPG resulted in ULVs whose <Ro> was found to be Clp dependent. The <Ro> of DMPG-doped ULVs remained unchanged over an extended period of time (at least 4 days), a good indication of their stability