Mimicry and mechanism in phospholipid models of membrane fusion

In spite of heroic efforts, phospholipid bilayer models of fusion do not mimic the cellular process closely enough to be confident that the cellular mechanism is being probed. Probably the experimental factors that are most difficult to control are the uniformity of the vesicles and the constraints that determine their behavior. In most conditions where fusion is triggered, the probability of bilayer mechanical rupture and leakage is increased. Confining that rupture to the contact area remains the most elusive characteristic of cell fusion to mimic. It may depend on fusogenic proteins. Some membrane characteristics, such as lipid asymmetry, may be crucial and may be determined biochemically, but they are difficult to duplicate in model systems. The contact-induced formation of nonbilayer lipid structures triggered by phosphatidylinositol turnover may offer some guidance in how the biochemical and required physical changes may be coupled.