Department of Theoretical and Applied Mechanics, Cornell University, Ithaca, NY 14853, USA.
Department of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY 14853, USA
J R Soc Interface. 2018 Jan;15(138). doi: 10.1098/rsif.2017.0818.
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 electrical impulse triggers the fusion process of pre-docked vesicles, leading to the formation of a fusion pore and subsequently resulting in 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 the vesicle and the plasma membrane. If the correct behaviour is chosen, the traverse time obtained is of the order of a few hundred milliseconds and lies within the experimentally obtained value of approximately 250 ms (Zenisek D, Steyer JA, Almers W. 2000 , 849-854 (doi:10.1038/35022500)). We hypothesize that there are two different force behaviours, which complies with the experimental findings of pre-fusion docking of synaptic vesicles at the ribbon synapses. The common theme in the proposed force models is that the driving force has to very rapidly increase or decrease with the amount of clamping.
突触囊泡融合是神经递质传递过程中的关键步骤。在带状突触中，通过带状结构和 SNARE 蛋白的介导，递质填充的囊泡预先停靠在突触处。电脉冲触发预先停靠的囊泡融合过程，导致融合孔的形成，随后递质释放到突触间隙中。在这项研究中，我们使用沿脂质膜的连续体模型和润滑理论来确定在流体动力的影响下突触囊泡的横越时间。我们发现，横越时间强烈依赖于驱动力随囊泡和质膜之间的间隙闭合而快速衰减或增长的速度。如果选择了正确的行为，横越时间约为几百毫秒，与实验获得的大约 250 毫秒的值（Zenisek D、Steyer JA、Almers W. 2000，849-854（doi：10.1038/35022500））相符。我们假设存在两种不同的力行为，这与带状突触中突触囊泡预先融合停靠的实验结果相符。所提出的力模型的共同主题是驱动力必须随夹紧量的增加或减少而迅速增加或减少。
