Unraveling the Influence of Geometry, Binding and Diffusion on Proteins in the Presynaptic Region*

The mobility of a protein is a key factor determining its availability for chemical reactions in a cell. It is influenced by many factors including the diffusion coefficient, binding to membranes and the geometry of the environment. In the presynaptic region of neurons, the latter varies widely between different synapses. Combined with the tremendous biological importance of this region it becomes a compelling quest to investigate mobility here.

In our work we use simulations to disentangle the interplay of the aforementioned factors. We demonstrate that the binding to synaptic vesicles and the cytoplasmic diffusion of the protein give rise to a specific length scale that determines whether the recovery of protein material is dominated by protein redistribution inside the synapse or via fluxes from the axon. This length scale is comparable to the size of the presynaptic region, which makes the interpretation of common experimental techniques for mobility measurements such as FRAP challenging. However, our simulations enable suggestions to circumvent pitfalls in Experiments.