Mechanisms of Membrane Fusion in Acidic Lipid-Cation Systems

Abstract

Since the original discovery that Ca⁺² converts small vesicles of phosphatidylserine into large sheets of spirally-wrapped membrane (1), the use of acidic lipid-divalent cation systems as models of membrane fusion has become widespread. There is now a wealth of experimental data available on the response of many different acidic lipids to a number of different cations under a wide variety of conditions (2). Many of these experimental investigations have utilized either a terbium-based fluorescence assay for mixing of vesicles contents (3) or a fluorescence energy transfer assay of membrane mixing (4). It is clear from results of both of these assays, as from early electron micrographs (1) that the membranes of many types of small vesicles merge with each other following divalent cation treatment, but the details of the pathway from initial vesicle to end product remain somewhat obscure. There is little doubt that fusion is involved at some stage, although the absence of precise terminology often leads to considerable ambiguity with regard to what kind of entity is fusing. The distinction is of some consequence, since the morphology of the species in which membranes become reconstructed places limits on the mechanical and chemical forces that may operate and hence influence the validity of the analogy that may be drawn to fusion of biological membranes. Thus, sentiment has been expressed for cautious extrapolation from these model systems to cells on the basis that extensive aggregation and leakage of contents, common features of model systems, cannot occur in cells (5–8).