Supplementary Information from Hydrodynamics govern the pre-fusion docking time of synaptic vesicle

Synaptic vesicle fusion is a crucial step in the neurotransmission process. Neurotransmitter-filled vesicles are pre-docked at the synapse, by the mediation of ribbon structures and SNARE proteins at the ribbon synapses. An electric impulse triggers the fusion process of pre-docked vesicle, leading to the formation of fusion pore and subsequently resulting into the release of neurotransmitter into the synaptic cleft. In this study, a continuum model of lipid membrane along with lubrication theory is used to determine the traverse time of the synaptic vesicle under the influence of hydrodynamic forces. We find that the traverse time is strongly dependent on how fast the driving force decays or grows with closure of the gap between vesicle and plasma membrane. If the right behaviour is chosen, the traverse time obtained is of the order of few hundred milliseconds and lies within the experimentally obtained value of approximately 250 ms (Zenisek D, Steyer JA, Almers W. 2000 Nature 406, 849–854. (doi:10.1038/35022500)). We hypothesize two different force behaviours, which comply with the experimental findings of pre-fusion docking of synaptic vesicle at the ribbon synapses. The common theme in the proposed force models is that driving force has to very rapidly increase or decrease with the amount of clamping.