Studying Membrane Fusion at the Molecular Level using a Biomimetic Model System

Abstract

Fusion of lipid bilayers, or membranes, is a ubiquitous process. It occurs in the cells of our body during cargo exchange by membrane vesicles and during viral infection, but also in industrial processes such as yeast production. While many proteins like SNAREs have been identified that play crucial roles in membrane fusion, the molecular mechanism of fusion remains unclear. This fascinating process is unexpectedly complex and our aim is to understand the details of this process using a biomimetic model system which has all the characteristics of natural membrane fusion; targeted docking, followed by lipid and content mixing in the absence of leakage.We developed a model system composed of a complementary pair of lipidated peptides able to form a heterodimeric coiled coil motif at the membrane interface similar to natural SNARE subunits. The different steps of membrane fusion are currently studied using biophysical and biochemical techniques with a special focus on peptide-peptide and peptide-lipid interactions. Unravelling of the molecular mechanism of membrane fusion using a multi-faceted approach of complementary techniques will result in a unique, in depth view of the process of membrane fusion.To date, it is a major challenge to achieve efficient and targeted liposome delivery directly into the cytoplasm of live cells, circumventing endocytotic pathways. In this respect, we recently studied and achieved membrane fusion between liposomes and live cells. Future applications are foreseen in drug delivery, nanoreactors and membrane engineering to name but a few.