Lipid-DNA complex formation: Reorganization and rupture of lipid vesicles in the presence of DNA as observed by cryoelectron microscopy

Cryoelectron microscopy has been used to study the reorganization of unilam ellar cationic lipid vesicles upon the addition of DNA. Unilamellar DNA-coa ted vesicles, as well as multilamellar DNA lipid complexes, could be observ ed. Also, DNA induced fusion of unilamellar vesicles was found. DNA appears to adsorb to the oppositely charged lipid bilayer in a monolayer of parall el helices and can act as a molecular "glue" enforcing close apposition of neighboring vesicle membranes. In samples with relatively high DNA content, there is evidence for DNA-induced aggregation and flattening of unilamella r vesicles. In these samples, multilamellar complexes are rare and contain only a small number of lamellae, At lower DNA contents, large multilamellar CL-DNA complexes, often with >10 bilayers, are formed, The multilamellar c omplexes in both types of sample frequently exhibit partially open bilayer segments on their outside surfaces. DNA seems to accumulate or coil near th e edges of such unusually terminated membranes. Multilamellar lipid-DNA com plexes appear to form by a mechanism that involves the rupture of an approa ching vesicle and subsequent adsorption of its membrane to a "template" ves icle or a lipid-DNA complex.