Stephens Thomas, Wu Zhanghan, Liu Jian
Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States of America. Equal contribution.
Phys Biol. 2017 May 23;14(3):035004. doi: 10.1088/1478-3975/aa6ad6.
Exocytosis is an important cellular process controlled by metabolic signaling. It involves vesicle fusion to the plasma membrane, followed by the opening of a fusion pore, and the subsequent release of the vesicular lumen content into the extracellular space. While most modeling efforts focus on the events leading to membrane fusion, how the vesicular membrane remodels after fusing to plasma membrane remains unclear. This latter event dictates the nature and the efficiency of exocytotic vesicular secretions, and is thus critical for exocytotic function. We provide a generic membrane mechanical model to systematically study the fate of post-fusion vesicles. We show that while membrane stiffness favors full-collapse vesicle fusion into the plasma membrane, the intravesicular pressure swells the vesicle and causes the fusion pore to shrink. Dimensions of the vesicle and its associated fusion pore further modulate this mechanical antagonism. We systematically define the mechanical conditions that account for the full spectrum of the observed vesicular secretion modes. Our model therefore can serve as a unified theoretical framework that sheds light on the elaborate control mechanism of exocytosis.
胞吐作用是一种由代谢信号控制的重要细胞过程。它涉及囊泡与质膜的融合，随后融合孔打开，囊泡腔内容物随后释放到细胞外空间。虽然大多数建模工作集中在导致膜融合的事件上，但囊泡膜与质膜融合后如何重塑仍不清楚。后一事件决定了胞吐性囊泡分泌的性质和效率，因此对胞吐功能至关重要。我们提供了一个通用的膜力学模型来系统地研究融合后囊泡的命运。我们表明，虽然膜刚度有利于完全塌陷的囊泡融合到质膜中，但囊泡内压力会使囊泡膨胀并导致融合孔收缩。囊泡及其相关融合孔的尺寸进一步调节这种机械拮抗作用。我们系统地定义了能够解释观察到的囊泡分泌模式全谱的力学条件。因此，我们的模型可以作为一个统一的理论框架，揭示胞吐作用的精细控制机制。
