The Kinetics of Non-Lamellar Phase Formation in DOPE-Me: Relevance to Biomembrane Fusion

The mechanism of the lamellar/inverted cubic (QII) phase transition is related to that of membrane fusion in lipid systems. N-Monomethylated dioleoylphosphatidylethanolamine (DOPE-Me) exhibits this transition and is commonly used to investigate the effects of exogenous substances, such as viral fusion peptides, on the mechanism of membrane fusion. We studied DOPE-Me phase behavior as a first step in evaluating the effects of membrane-spanning peptides on inverted phase formation and membrane fusion. These measurements show that: a) the onset temperatures for QII and inverted hexagonal (HII) phase formation both are temperature scan rate-dependent; b) longer pre-incubation times at low temperature and lower temperature scan rates favor formation of the QII phase; and c) in temperature-jump experiments between 61 and 65°C, the meta-stable HII phase forms initially, and disappears slowly while the QII phase develops. These observations are rationalized in the context of a mechanism for both the lamellar/non-lamellar phase transition and the related process of membrane fusion.