Polymer-induced membrane fusion: potential mechanism and relation to cell fusion events

Poly(ethylene glycol) (PEG) is used widely to mediate cell-cell fusion in the production of somatic cell hybrids and in the fusion injection of macromolecules into cultured cells from erythrocytes or liposomes. However, little is known about the mechanisms by which PEG induces fusion of cell membranes, making its use much more an art than a science. This article considers possible molecular events involved in biomembrane fusion and summarizes what we have learned about these in recent years from studies of fusion of well-defined model membranes. In addition, it recounts observations made over the past several years about the process of PEG-mediated fusion of model membranes. These observations have defined the process to an extent sufficient to allow us to propose a model for the molecular events involved in the process. It is suggested that dehydration leads to asymmetry in the lipid packing pressure in the two leaflets of the membrane bilayer leading to formation of a single bilayer septum at a point of close apposition of two membranes. The single bilayer septum then decays during formation of the initial fusion pore. Agents that enhance or alleviate the dehydration-induced asymmetric packing stress will favor or inhibit fusion. Although the proposed picture is consistent with much accumulated data, it is not yet proven; experiments must now be devised to test its details. Finally, the proposed model is discussed in terms of potential implications for the mechanisms available to a cell in controlling more complex in vivo cell fusion processes such as endocytosis, exocytosis, protein sorting/transport, and viral budding/infection.