The modified stalk mechanism of lamellar/inverted phase transitions and its implications for membrane fusion. 1999

D P Siegel
Chemistry Department, The Ohio State University, Columbus, Ohio 43210 USA. dsiegel@chemistry.ohio-state.edu

A model of the energetics of lipid assemblies (Siegel. 1993. Biophys. J. 65:2124-2140) is used to predict the relative free energy of intermediates in the transitions between lamellar (Lalpha) inverted hexagonal (HII), and inverted cubic (QII) phases. The model was previously used to generate the modified stalk theory of membrane fusion. The modified stalk theory proposes that the lowest energy structures to form between apposed membranes are the stalk and the transmonolayer contact (TMC), respectively. The first steps in the Lalpha/HII and Lalpha/QII phase transitions are also intermembrane events: bilayers of the Lalpha phase must interact to form new topologies during these transitions. Hence the intermediates in these phase transitions should be similar to the intermediates in the modified stalk mechanism of fusion. The calculations here show that stalks and TMCs can mediate transitions between the Lalpha, QII, and HII phases. These predictions are supported by studies of the mechanism of these transitions via time-resolved cryoelectron microscopy (. Biophys. J. 66:402-414; Siegel and Epand. 1997. Biophys. J. 73:3089-3111), whereas the predictions of previously proposed transition mechanisms are not. The model also predicts that QII phases should be thermodynamically stable in all thermotropic lipid systems. The profound hysteresis in Lalpha/QII transitions in some phospholipid systems may be due to lipid composition-dependent effects other than differences in lipid spontaneous curvature. The relevant composition-dependent properties are the Gaussian curvature modulus and the membrane rupture tension, which could change the stability of TMCs. TMC stability also influences the rate of membrane fusion of apposed bilayers, so these two properties may also affect the fusion rate in model membrane and biomembrane systems. One way proteins catalyze membrane fusion may be by making local changes in these lipid properties. Finally, although the model identifies stalks and TMCs as the lowest energy intermembrane intermediates in fusion and lamellar/inverted phase transitions, the stalk and TMC energies calculated by the present model are still large. This suggests that there are deficiencies in the current model for intermediates or intermediate energies. The possible nature of these deficiencies is discussed.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
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
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
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D001703 Biophysics The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things. Mechanobiology
D013816 Thermodynamics A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed) Thermodynamic
D055592 Biophysical Phenomena The physical characteristics and processes of biological systems. Biophysical Concepts,Biophysical Processes,Biophysical Phenomenon,Biophysical Process,Biophysical Concept,Concept, Biophysical,Concepts, Biophysical,Phenomena, Biophysical,Phenomenon, Biophysical,Process, Biophysical,Processes, Biophysical
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