Katsov K, Müller M, Schick M
Materials Research Laboratory, University of California, Santa Barbara, California, USA.
Biophys J. 2006 Feb 1;90(3):915-26. doi: 10.1529/biophysj.105.071092. Epub 2005 Nov 4.
We use self-consistent field theory to determine structural and energetic properties of intermediates and transition states involved in bilayer membrane fusion. In particular, we extend our original calculations from those of the standard hemifusion mechanism, which was studied in detail in the first article of this series, to consider a possible alternative to it. This mechanism involves non-axial stalk expansion, in contrast to the axially symmetric evolution postulated in the classical mechanism. Elongation of the initial stalk facilitates the nucleation of holes and leads to destabilization of the fusing membranes via the formation of a stalk-hole complex. We study properties of this complex in detail, and show how transient leakage during fusion, previously predicted and recently observed in experiment, should vary with lipid architecture and tension. We also show that the barrier to fusion in the alternative mechanism is lower than that of the standard mechanism by a few k(B)T over most of the relevant region of system parameters, so that this alternative mechanism is a viable alternative to the standard pathway. We emphasize that any mechanism, such as this alternative one, which affects, even modestly, the line tension of a hole in a membrane, affects greatly the ability of that membrane to undergo fusion.
我们使用自洽场理论来确定双层膜融合过程中涉及的中间体和过渡态的结构与能量性质。特别地，我们将最初的计算从本系列第一篇文章中详细研究的标准半融合机制扩展到考虑其一种可能的替代机制。与经典机制中假设的轴对称演化不同，这种机制涉及非轴向柄部扩展。初始柄部的伸长促进了孔洞的成核，并通过形成柄 - 孔复合物导致融合膜的不稳定。我们详细研究了这种复合物的性质，并展示了融合过程中先前预测且最近在实验中观察到的瞬时泄漏如何随脂质结构和张力而变化。我们还表明，在系统参数的大部分相关区域中，替代机制中的融合势垒比标准机制的低几个(k_BT)，因此这种替代机制是标准途径的一个可行替代方案。我们强调，任何机制，比如这种替代机制，即使对膜中孔洞的线张力有适度影响，也会极大地影响该膜进行融合的能力。
