Fusion mechanisms of asymmetric lipid vesicles and membranes mimicking the cell wall and endosome

Communication and transfer of material between cells is a fundamental process in cell biology. Nature uses vesicles for such cell-to-cell communication in the form of extracellular vesicles (EVs). EVs are innately biocompatible and have huge potential in therapeutics and diagnostics, thanks in part to the fact that they possess many functionally relevant moieties including nucleic acid cargoes, proteins, and surface receptors, whose roles in EV activity and biodistribution have been well studied. However, less is known about the role of the lipids, although it is has been shown that EV populations have significantly different lipid distributions depending on cell line and biogenesis. The uptake of EVs and other lipid particles is widely accepted as varying across cell types. While this is in part due to surface markers, it is also due to the lipid composition. In my group we are developing vesicles with asymmetric distribution of lipids across the membrane, which mimic the lipid compositions found in EVs. These synthetic asymmetric vesicles will allow us to decouple the role of lipids in such biological processes. In this experiment, we will use DNA to tether these asymmetric vesicles to the surface of free-floating lipid bilayers representing lipid compositions of cell membranes and intracellular compartments, and study their fusion processes.