To fuse or not to fuse: the effects of electrostatic interactions, hydrophobic forces, and structural amphiphilicity on protein-mediated membrane destabilization

The development of lipid-based delivery vehicles for therapeutic molecules has become a topic of intense research. Recently, much of this effort has been directed towards mimicking the characteristics of viruses that give them an advantage for the delivery of genetic medicines. One of the most desirable properties of viral-based vectors is the ability to promote the destabilization of the host cell membrane to allow the entry of the genetic medicine into the target cell. This has been found to be largely controlled by the coat proteins on the surface of enveloped viruses. Although the exact mechanism by which proteins involved in the fusion process are able to promote the destabilization of membranes has yet to be elucidated, much understanding based upon information gained from a wide variety of studies is advancing the state of knowledge in this area. Parameters such as hydrophobic and electrostatic interactions as well as structural amphiphilicity, control to a large extent, the nature of the interaction of proteins with membranes. Thus, membrane fusion is mediated primarily by these forces acting in concert with one another. Ultimately, the knowledge gained from these studies will help to develop the ideal delivery system for the next generation of therapeutics. (C) 1999 Elsevier Science B.V. All rights reserved.