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Adv Drug Deliv Rev. 1999 Aug 20;38(3):207-232.

Lipid vesicles and membrane fusion.

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1
Medizinische Biophysik, Technische Universit√§t M√ľnchen, Klinikum r.d.I., Ismaningerstrasse 22, D-81675, Munich, Germany

Abstract

Membrane fusion is essential for cell survival and has attracted a great deal of both theoretical and experimental interest. Fluorescence (de)quenching measurements were designed to distinguish between bilayermerging and vesicle-mixing. Theoretical studies and various microscopic and diffraction methods have elucidated the mechanism of membrane fusion. These have revealed that membrane proximity and high defect density in the adjacent bilayers are the only prerequisites for fusion. Intermediates, such as stalk or inverse micellar structures can, but need not, be involved in vesicle fusion. Nonlamellar phase creation is accompanied by massive membrane fusion although it is not a requirement for bilayer merging. Propensity for membrane fusion is increased by increasing the local membrane disorder as well by performing manipulations that bring bilayers closer together. Membrane rigidification and enlarged bilayer separation opposes this trend. Membrane fusion is promoted by defects created in the bilayer due to the vicinity of lipid phase transition, lateral phase separation or domain generation, high local membrane curvature, osmotic or electric stress in or on the membrane; the addition of amphiphats or macromolecules which insert themselves into the membrane, freezing or other mechanical membrane perturbation have similar effects. Lowering the water activity by the addition of water soluble polymers or by partial system dehydration invokes membrane aggregation and hence facilitates fusion; as does the membrane charge neutralization after proton or other ion binding to the lipids and intermembrane scaffolding by proteins or other macromolecules. The alignment of defect rich domains and polypeptides or protein binding is pluripotent: not only does it increase the number of proximal defects in the bilayers, it triggers the vesicle aggregation and is fusogenic. Exceptions are the bound molecules that create steric or electrical barriers between the membranes which prevent fusion. Membrane fusion can be non-leaky but it is very common to lose material from the vesicle interior during the later stages of membrane unification, that is, after a few hundred microseconds following the induction of fusion.

PMID:
10837758

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