Lipids favoring inverted phase enhance the ability of aerolysin to permeabilize liposome bilayers

Channel formation by the bacterial toxin aerolysin follows oligomerization of the protein to produce heptamers that are capable of inserting into lipi d bilayers. How insertion occurs is not understood, not only for aerolysin but also for other proteins that can penetrate membranes. We have studied a erolysin channel formation by measuring dye leakage from large unilamellar egg phosphatidylcholine vesicles containing varying amounts of other lipids . The rate of leakage was enhanced in a dose-dependent manner by the presen ce of phosphatidylethanolamine, diacylglycerol, cholesterol, or hexadecane, all of which are known to favor a lamellar-to-inverted hexagonal (L-H) pha se transition. Phosphatidylethanolamine molecular species with low L-H tran sition temperatures had the largest effects on aerolysin activity. In contr ast, the presence in the egg phosphatidylcholine liposomes of lipids that a re known to stabilize the lamellar ph ase, such as sphingomyelin and satura ted phosphatidylcholines, reduced the rate of channel formation, as did the presence of lysophosphatidylcholine, which favors positive membrane curvat ure. When two different: lipids that favor hexagonal phase were present wit h egg PC in the liposomes, their stimulatory effects were additive. Phospha tidylethanolamine and lysophosphatidylcholine canceled each other's effect on channel formation.