Biomaterial Database

Effect of single chain lipids on phospholipase C-promoted vesicle fusion. A test for the stalk hypothesis of membrane fusion. 1998

G Basáñez, and F M Goñi, and A Alonso

Departamento de Bioquímica, Universidad del País Vasco, Bilbao, Spain.

The effect of low proportions (up to 5 mol %) of single-chain lipids on phospholipase C-promoted fusion of large unilamellar vesicles has been investigated with the aim of testing the so-called stalk model of membrane fusion. This model is known in two main versions, the one originally published by Kozlov and Markin [Kozlov, M. M. and Markin, V. S. (1983) Biofizika 28, 255-261] and what is known as the "modified stalk model" [Siegel, D. P. (1993) Biophys. J. 65, 2124-2140], that differ in a number of predictions. In the view of the latter author, hydrocarbons or other nonpolar lipids should help fusion by decreasing the interstitial energy of the stalk connecting the two apposed bilayers. We show that small amounts of hexadecane or squalene increase significantly the fusion rates in our system. Changes in monolayer curvature are the object of different predictions by the original and modified stalk theories. According to the original form, fusion would be promoted by lipids inducing a negative curvature in the closest (cis) monolayers of the fusing membranes and inhibited by the same lipids in the trans monolayers; the opposite would happen with lipids inducing a positive curvature. The modified stalk model predicts that fusion is helped by increasing the negative curvature of both monolayers. In our system, symmetrically distributed arachidonic acid, which increases the negative curvature, enhances lipid and content mixing, and the opposite is found with symmetrically distributed lysophosphatidylcholine or palmitoylcarnitine, which facilitate a positive monolayer curvature. In addition, fluorescence polarization and 31P NMR studies of the lamellar-to-isotropic (Q224 cubic) thermotropic transition of a lipid mixture corresponding to our liposomal composition reveal that all lipids that facilitate fusion decrease the transition temperature, while fusion inhibitors increase the transition temperature. Moreover, fusion (content mixing) rates show a maximum at the lamellar-to-isotropic transition temperature. These observations support the involvement of inverted lipid structures, as occurring in the inverted cubic phases, in membrane fusion. All these data are in full agreement with the stalk model of membrane fusion, particularly in its modified version.

UI	MeSH Term	Description	Entries
D008051	Lipid Bilayers	Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.	Bilayers, Lipid,Bilayer, Lipid,Lipid Bilayer
D008244	Lysophosphatidylcholines	Derivatives of PHOSPHATIDYLCHOLINES obtained by their partial hydrolysis which removes one of the fatty acid moieties.	Lysolecithin,Lysolecithins,Lysophosphatidylcholine
D008561	Membrane Fusion	The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes.	Fusion, Membrane,Fusions, Membrane,Membrane Fusions
D008563	Membrane Lipids	Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation.	Cell Membrane Lipid,Cell Membrane Lipids,Membrane Lipid,Lipid, Cell Membrane,Lipid, Membrane,Lipids, Cell Membrane,Lipids, Membrane,Membrane Lipid, Cell,Membrane Lipids, Cell
D008823	Micelles	Particles consisting of aggregates of molecules held loosely together by secondary bonds. The surface of micelles are usually comprised of amphiphatic compounds that are oriented in a way that minimizes the energy of interaction between the micelle and its environment. Liquids that contain large numbers of suspended micelles are referred to as EMULSIONS.	Micelle
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D010714	Phosphatidylethanolamines	Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to an ethanolamine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and ethanolamine and 2 moles of fatty acids.	Cephalin,Cephalins,Ethanolamine Phosphoglyceride,Ethanolamine Phosphoglycerides,Ethanolamineglycerophospholipids,Phosphoglyceride, Ethanolamine,Phosphoglycerides, Ethanolamine
D010738	Type C Phospholipases	A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.	Lecithinase C,Phospholipase C,Phospholipases, Type C,Phospholipases C
D002784	Cholesterol	The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.	Epicholesterol
D004075	Diglycerides	Glycerides composed of two fatty acids esterified to the trihydric alcohol GLYCEROL. There are two possible forms that exist: 1,2-diacylglycerols and 1,3-diacylglycerols.	Diacylglycerol,Diacylglycerols