Field of Theoretical and Applied Mechanics, Cornell University, Ithaca, NY, USA.
J R Soc Interface. 2012 Jul 7;9(72):1555-67. doi: 10.1098/rsif.2011.0827. Epub 2012 Jan 18.
Release of neurotransmitters from nerve terminals occurs by fusion of synaptic vesicles with the plasma membrane, and this process is highly regulated. Although major molecular components that control docking and fusion of vesicles to the synaptic membrane have been identified, the detailed mechanics of this process is not yet understood. We have developed a mathematical model that predicts how adhesion forces imposed by docking and fusion molecular machinery would affect the fusion process. We have computed the membrane stress that is produced by adhesion-driven vesicle bending and find that it is compressive. Further, our computations of the membrane curvature predict that strong adhesion can create a metastable state with a partially opened pore that would correspond to the 'kiss and run' release mode. Our model predicts that the larger the vesicle size, the more likely the metastable state with a transiently opened pore. These results contribute to understanding the mechanics of the fusion process, including possible clamping of the fusion by increasing molecular adhesion, and a balance between 'kiss and run' and full collapse fusion modes.
神经递质从神经末梢释放是通过突触小泡与质膜融合来实现的，这个过程受到高度调控。尽管已经确定了控制囊泡与突触膜对接和融合的主要分子成分，但这个过程的详细机制仍不清楚。我们已经开发了一个数学模型，该模型可以预测由对接和融合分子机制施加的粘附力如何影响融合过程。我们已经计算了由粘附驱动的囊泡弯曲产生的膜应力，发现它是压缩性的。此外，我们对膜曲率的计算表明，强烈的粘附可以产生一个具有部分打开的孔的亚稳态，这将对应于“亲吻和跑开”释放模式。我们的模型预测，囊泡尺寸越大，具有暂时打开的孔的亚稳态的可能性就越大。这些结果有助于理解融合过程的力学，包括通过增加分子粘附来夹紧融合，以及“亲吻和跑开”和完全塌陷融合模式之间的平衡。
