Reversibility of structural rearrangements in the negative vesicular membrane upon electrostatic adsorption/desorption of the polycation

Abstract

Interaction of small unilamellar vesicles (SUVs), composed of negative diphosphatidylglycerol (cardiolipin, CL(2-)) and neutral dipalmitoylphosphatidylcholine (DPPC), with poly(N-ethyl-4-vinylpyridinium bromide) (PEVP) was studied in water solution above and below the vesicular membrane melting point by means of differential scanning calorimetry, photon correlation spectroscopy, microelectrophoresis, conductometry, and fluorescence techniques. It has been found that CL(2-) species are homogeneously distributed within DPPC-CL(2-) SUV membrane leaflets and between them. Interaction of PEVP with DPPC-CL(2-) SUVs led to drastic structural rearrangements in the membrane if it was in the fluid state (liquid SUVs). Negative CL(2-) molecules migrated from the inner to the outer membrane leaflet and segregated in the vicinity of adsorbed PEVP chains. In addition, PEVP adsorption terminated completely the exchange of lipid molecules between the SUVs. At the same time, the integrity of liquid SUVs contacting PEVP remained unchanged. Since the interaction of PEVP with liquid SUVs was predominantly electrostatic in nature, the polycation could be completely removed from the vesicular membrane by addition of an excess of polyacrylic acid (PAA) polyanions forming a more stable electrostatic complex with PEVP. Removal of PEVP resulted in complete resumption of the original distribution of lipids in lateral and transmembrane directions as well as intervesicular lipid exchange. In contrast, PEVP interacting with DPPC-CL(2-) SUVs formed defects in the vesicular membrane if it was in the gel state (solid SUVs). Such interaction was contributed not only by electrostatic but most likely by hydrophobic interactions involving the defected membrane sites. PEVP kept contacting solid SUVs in the presence of an abundant amount of PAA. The established phenomena may be important for understanding the biological effects of polycations.

The Influence of the Chain Length of Polycations on their Complexation with Anionic Liposomes

“…It has been showne arlier that CL 2À molecules are uniformly (fifty-fifty) distributed between the outera nd the inner leaflets in the membrane of both CL 2À /EL liposomes and CL 2À /DPPC liposomes. [10] The calorimetric curve for DPPC liposomes deprived of CL 2À is represented in Figure 4( curve 5).…”

Polyelectrolyte-coated liposomes: Stabilization of the interfacial complexes

“…PL was shown not to induce lipid flip-flop but, instead, to form salt bonds with only the outer CL 2− molecules (one-half of the total amount distributed within the membrane of EL/CL 2− liposomes). In summary, P2 induces a CL 2− flip-flop in liquid lipid membranes, but PL does not [26,36,56]. A rationale for P2-induced flip-flop of CL 2− , but an absence of such with PL, may reside in the structures of the interfacial polycation/lipid complexes.…”

“…However, in spite of strong, nearly quantitative electrostatic adsorption of polycations onto the surface of anionic liposomes, the polycations were shown to be completely removed by complexation with added anionic homopolymers [18,23,26,34,35,36]. This means that both synthetic and natural polyanions are able to disrupt multilayer formation and effect its integrity in biological environments.…”

“…The monodispersity of the liposomes is obvious. The key point is that the 100% electrostatic complexation of CL 2− by adsorbed P2 could only happen if there was fast transmembrane migration of CL 2− ions from the inner to outer leaflet of the liquid liposomal membrane [26,36,39].…”

Liposome solubilization induced by complexation with dimeric β-cyclodextrin

“…In fact, polylysin induces cell fusion at a low concentration because of electrostatic binding to anionic cell surfaces [22]. Similarly, cationic polypeptide is adsorbed on the membrane of negative vesicles [23], permeation of DNA through cell membranes [20]. Although dimeric b-CD has no cationic charge, the dimeric conformation can provide the appropriate space to bind PDA vesicles.…”