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 (Ca ²⁺) and/or the negatively charged lipid, dimyristoyl phosphatidylglycerol (DMPG). For dilute solutions (lipid concentration ≤1 wt %), spontaneously forming unilamellar vesicles (ULVs) were found, and their polydispersity was determined to be ∼20%. The stability of the Ca ²⁺- or DMPG-doped ULVs was monitored over a period of 4 days and their structural parameters (e.g., average outer radius, 〈R _o〉) were found to be insensitive to the lipid concentration (C_1p). However, doping the dimyristoyl/ dihexanoyl system with both Ca²⁺ and DMPG resulted in ULVs whose 〈R_o〉 was found to be C_1p of DMPG-doped ULVs remained unchanged over an extended period of time (at least 4 days), a good indication of their stability.