To fuse, membranes must bend. The energy of the unknown bent intermediates of biological fusion in diverse physiological processes depends on the ability of membrane lipids support the required curvatures. We have studied the effects of membrane lipid composition on the rates of fusion reaction. Lipids of the different molecular shapes such as inverted cone-shaped lysophosphatidylcholine, LPC, and cone- shaped arachidonic acid, AA, were added exogenously to membranes to alter their propensity to bend. Addition of LPC to contacting monolayers of cell membranes inhibited low pH triggered cell-cell fusion mediated by the specialized envelope proteins of baculovirus (gp64) and influenza virus (hemagglutinin). In contrast, AA promoted these fusion reactions. Modulation of membrane lipid composition reversibly affected fusion (inhibited or promoted) at a stage of actual merger of membrane lipid bilayers which follow the triggering of fusion. To elucidate the mechanisms of lipid bilayer fusion in the well defined model system we studied the fusion of phospholipid vesicles to planar phospholipid bilayer membranes. Two distinct fusion stages, hemi- and complete fusion (i.e., membranes' lipid mixing without and with fusion pore formation, respectively) were established. Hemifusion was prevented by adding inverted cone-shaped LPC to contacting monolayers of two fusing membranes. In contrast, fusion pore formation depended on the composition of distal monolayers: LPC promoted and cone-shaped AA inhibited complete fusion. Thus, lipids differentially modulate membrane fusion by stages according to lipid shape and place. The similarity between effects of the membrane lipid composition obtained for fusion of model lipid membranes and those for biological membrane fusion supports the hypothesis that stalk (local connection between two membranes leading to membrane hemifusion) and pore types of fusion intermediates may be involved in the biological fusion.
| Zaitseva, E; Chernomordik, L (2012) Fusion stage of dengue virus entry: mechanisms and assays. Microsc Microanal 18 Suppl 2:52-3 |
| Rafikova, Elvira R; Melikov, Kamran; Ramos, Corinne et al. (2009) Transmembrane protein-free membranes fuse into xenopus nuclear envelope and promote assembly of functional pores. J Biol Chem 284:29847-59 |
| Chernomordik, Leonid V; Kozlov, Michael M (2008) Mechanics of membrane fusion. Nat Struct Mol Biol 15:675-83 |
| Sapir, Amir; Avinoam, Ori; Podbilewicz, Benjamin et al. (2008) Viral and developmental cell fusion mechanisms: conservation and divergence. Dev Cell 14:11-21 |
| Sapir, Amir; Choi, Jaebok; Leikina, Evgenia et al. (2007) AFF-1, a FOS-1-regulated fusogen, mediates fusion of the anchor cell in C. elegans. Dev Cell 12:683-98 |
| Zhukovsky, Mikhail A; Markovic, Ingrid; Bailey, Austin L (2007) Influence of calcium on lipid mixing mediated by influenza hemagglutinin. Arch Biochem Biophys 465:101-8 |
| Efrat, Avishay; Chernomordik, Leonid V; Kozlov, Michael M (2007) Point-like protrusion as a prestalk intermediate in membrane fusion pathway. Biophys J 92:L61-3 |
| Gattegno, Tamar; Mittal, Aditya; Valansi, Clari et al. (2007) Genetic control of fusion pore expansion in the epidermis of Caenorhabditis elegans. Mol Biol Cell 18:1153-66 |
| Ramos, Corinne; Rafikova, Elvira R; Melikov, Kamran et al. (2006) Transmembrane proteins are not required for early stages of nuclear envelope assembly. Biochem J 400:393-400 |
| Chernomordik, Leonid V; Melikov, Kamran (2006) Are there too many or too few SNAREs in proteoliposomes? Biophys J 90:2657-8 |
Showing the most recent 10 out of 22 publications
