Lipid plasticity and its relevance for critical biological processes involving membrane reorganization

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The cell membrane is of singular importance for life since it acts as a barrier to the cell environment and controls what goes in and what goes out. Moreover, membrane reorganization by fusion and fission is central to a number of biological processes, such as fertilization, viral infection, vesicle trafficking and cell division. Cell membranes are mainly composed of lipids, forming the framework of the membranes, and proteins, responsible for the biological activities, such as enzymatic processes. The phospholipids constitute the most important class of lipids found in Nature. These molecules are amphipatic, i.e. they have a hydrophilic part, commonly called the polar head, and a hydrophobic part composed of two aliphatic chains. When phospholipids are mixed with water in adequate concentrations, hydrophobic forces cause the aliphatic chains regroup together with the polar heads facing the water. Biological membranes are predominantly arranged as bilayers. Also, proteins with a hydrophobic nature bind to membranes. Recent work from our group shown that a peptide embedded in a bilayer has the ability to change the conformation or "shape" of the lipids. Based on this peptide-induced effect on the lipids, we then proposed the concept of "dynamically induced shape". This concept recognizes that the bilayer membrane is a conformationally plastic and dynamical environment that reacts in a complex way to the presence of impurities or a physical stress. The main objective of the proposed research program is to investigate membrane plasticity for two cases of high biological relevance, membrane fusion from viral infection and membrane fission by antimicrobial peptides. Complementary tools from structural bioinformatics will be used to achieve the goals of this innovative research program.