Temperature-dependence of cationic lipid bilayer intermixing: possible role of interdigitation

In this work, we investigated the properties of a fusogenic cationic lipid, diC14-amidine, and show that this lipid possesses per se the capacity to adopt either an interdigitated structure (below and around its transition temperature) or a lamellar structure (above the transition temperature). To provide experimental evidence of this lipid bilayer organization, phospholipids spin-labeled at different positions of the hydrocarbon chain were incorporated into the membrane and their electron spin resonance (ESR) spectra were recorded at different temperatures. For comparison, similar experiments were performed with dimyristoyl phosphatidylcholine, a zwitterionic lipid (DMPC) which adopts a bilayer organization over a broad temperature range. Lipid mixing between diC14-amidine and asolectin liposomes was more efficient below (10-15 °C) than above the transition temperature (above 25 °C). This temperature-dependent "fusogenic" activity of diC14-amidine liposomes is opposite to what has been observed so far for peptides or virus-induced fusion. Altogether, our data suggest that interdigitation is a highly fusogenic state and that interdigitation-mediated fusion occurs via an unusual temperature-dependent mechanism that remains to be deciphered.