Dynamics of fusion pores connecting membranes of different tensions

Dynamics of fusion pores connecting membranes of different tensions
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DOI:
10.1016/s0006-3495(00)76771-3
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发表时间:
2000-05-01
影响因子:
3.4
通讯作者:
Cohen, FS
Cohen, FS
中科院分区:
生物学3区
文献类型:
--
作者:
Chizmadzhev, YA;Kuzmin, PI;Cohen, FS

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阐明了连接生物或脂类双层膜的融合孔扩张的能量学基础。随着孔的扩大而使膜变形所需的能量,与融合蛋白的某种作用相结合,必须决定孔的生长。考虑了不同张力下两种均质熔合膜的孔生长动力学。严格地证明,孔的生长可以通过将孔视为在由膜的粘度决定的介质中运动的准粒子来定量描述。运动会受到拉力、弯曲力和粘性力的影响。利用拉格朗日方程计算了单层内和单层间摩擦引起的耗散作用下的孔道动力学和通过孔道的脂类流动。这些计算表明,抑制孔扩张的能垒只取决于张力的总和;熔合膜之间的张力差异是无关的。相反,通过融合孔的脂流量取决于张力差,但与总和无关。因此,孔的生长不受从一个膜到另一个膜的张力驱动的脂通量的影响。本研究的计算解释了如何通过小泡的渗透性膨胀增加张力导致小泡和平面双层膜之间的毛孔扩大。同样,在生物系统中,分泌颗粒融合后的膨胀可以促进胞吐过程中的毛孔扩大。计算还表明,孔的扩张可能是由孔的延长引起的,而延长可能是由融合蛋白促进的。
The energetics underlying the expansion of fusion pores connecting biological or lipid bilayer membranes is elucidated. The energetics necessary to deform membranes as the pore enlarges, in some combination with the action of the fusion proteins, must determine pore growth. The dynamics of pore growth is considered for the case of two homogeneous fusing membranes under different tensions. It is rigorously shown that pore growth can be quantitatively described by treating the pore as a quasiparticle that moves in a medium with a viscosity determined by that of the membranes. Motion is subject to tension, bending, and viscous forces. Pore dynamics and lipid flow through the pore were calculated using Lagrange's equations, with dissipation caused by intra- and intermonolayer friction. These calculations show that the energy barrier that restrains pore enlargement depends only on the sum of the tensions; a difference in tension between the fusing membranes is irrelevant. in contrast, lipid flux through the fusion pore depends on the tension difference but is independent of the sum. Thus pore growth is not affected by tension-driven lipid flux from one membrane to the other. The calculations of the present study explain how increases in tension through osmotic swelling of vesicles cause enlargement of pores between the vesicles and planar bilayer membranes. In a similar fashion, swelling of secretory granules after fusion in biological systems could promote pore enlargement during exocytosis. The calculations also show that pore expansion can be caused by pore lengthening; lengthening may be facilitated by fusion proteins.