Short-chain alcohols promote an early stage of membrane hemifusion.
Hemifusion, the linkage of contacting lipid monolayers of two membranes before the opening of a fusion pore, is hypothesized to proceed through the formation of a stalk intermediate, a local and strongly bent connection between membranes. When the monolayers' propensity to bend does not support the stalk (e.g., as it is when lysophosphatidylcholine is added), hemifusion is inhibited. In contrast, short-chain alcohols, reported to affect monolayer bending in a manner similar to that of lysophosphatidylcholine, were here found to promote hemifusion between fluorescently labeled liposomes and planar lipid bilayers. Single hemifusion events were detected by fluorescence microscopy. Methanol or ethanol (1.2-1.6 w/w %) added to the same compartment of the planar bilayer chamber as liposomes caused a 5-50 times increase in the number of hemifusion events. Alcohol-induced hemifusion was inhibited by lysophosphatidylcholine. Promotion of membrane hemifusion by short-chain alcohol was also observed for cell-cell fusion mediated by influenza virus hemagglutinin (HA). Alcohol promoted a fusion stage subsequent to the low pH-dependent activation of HA. We propose that binding of short-chain alcohol to the surface of membranes promotes hemifusion by facilitating the transient breakage of the continuity of each of the contacting monolayers, which is required for their subsequent merger in the stalk intermediate.
Chanturiya
A
A
Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 USA.
Leikina
E
E
Zimmerberg
J
J
Chernomordik
L V
LV
D020001:1-Butanol / Q000378:metabolism / Q000494:pharmacology; D016475:3T3 Cells; D000438:Alcohols / Q000737:chemistry* / Q000378:metabolism*; D000473:Alkanes / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002459:Cell Fusion / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology; D004553:Electric Conductivity; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism / Q000494:pharmacology; D008561:Membrane Fusion / Q000187:drug effects; D000432:Methanol / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D011409:Propylene Glycols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D000438:Alcohols; D000473:Alkanes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008051:Lipid Bilayers; D008081:Liposomes; D008244:Lysophosphatidylcholines; D011409:Propylene Glycols; C024713:n-tetradecane; D000431:Ethanol; D020001:1-Butanol; D002784:Cholesterol; D000432:Methanol