Heterogeneity of early intermediates in cell-liposome fusion mediated by influenza hemagglutinin.
To explore early intermediates in membrane fusion mediated by influenza virus hemagglutinin (HA) and their dependence on the composition of the target membrane, we studied lipid mixing between HA-expressing cells and liposomes containing phosphatidylcholine (PC) with different hydrocarbon chains. For all tested compositions, our results indicate the existence of at least two types of intermediates, which differ in their lifetimes. The composition of the target membrane affects the stability of fusion intermediates at a stage before lipid mixing. For less fusogenic distearoyl PC-containing liposomes at 4 degrees C, some of the intermediates inactivate, and no intermediates advance to lipid mixing. Fusion intermediates that formed for the more fusogenic dioleoyl PC-containing liposomes did not inactivate and even yielded partial lipid mixing at 4 degrees C. Thus, a more fusogenic target membrane effectively blocks nonproductive release of the conformational energy of HA. Even for the same liposome composition, HA forms two types of fusion intermediates, dissimilar in their stability and propensity to fuse. This diversity of fusion intermediates emphasizes the importance of local membrane composition and local protein concentration in fusion of heterogeneous biological membranes.
Zhukovsky
Mikhail A
MA
Laboratory of Cellular and Molecular Biophysics, Section on Membrane Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Mikhail_Zhukovsky@dfci.harvard.edu
Leikina
Eugenia
E
Markovic
Ingrid
I
Bailey
Austin L
AL
Chernomordik
Leonid V
LV
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000494:pharmacology*; D007668:Kidney / Q000737:chemistry* / Q000502:physiology*; D008081:Liposomes / Q000737:chemistry*; D008561:Membrane Fusion / Q000187:drug effects / Q000502:physiology*
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008081:Liposomes