Erwin Neher
Exocytosis and endocytosis of synaptic vesicles (SVs) are central processes of synaptic function. We investigate the role of proteins such as SNAREs and dynamin. Our hypothesis is: (i) proteins lower the free energy barriers of fusion and fission through force transmission and membrane-mediated interactions, and (ii) they impose mechanical as well as chemical boundary conditions for topological changes of the membrane.
Using self-consistent field theory (SCFT), parameterized by molecular simulations and experimental data, we determine minimum free-energy pathways and quantify the energy barriers as a function of lipid, protein, and solvent parameters. Fusion and fission rates are calculated using appropriate reaction coordinates. By varying the number and spatial arrangement of the proteins, we analyze release mechanisms and compare the results with experimental data. In this way, we gain insights into the mechanisms and rates of exo- and endocytosis, which are incorporated into more coarse-grained synaptic models.



