Smeijers A F, Pieterse K, Markvoort A J, Hilbers P A J
Department of Biomedical Engineering, Technische Universiteit Eindhoven, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
J Phys Chem B. 2006 Jul 13;110(27):13614-23. doi: 10.1021/jp062012y.
Molecular transport between organelles is predominantly governed by vesicle fission and fusion. Unlike experimental vesicles, the fused vesicles in molecular dynamics simulations do not become spherical readily, because the lipid and water distribution is inappropriate for the fused state and spontaneous amendment is slow. Here, we study the hypothesis that enhanced transport across the membrane of water, lipids, or both is required to produce spherical vesicles. This is done by adding several kinds of model proteins to fusing vesicles. The results show that equilibration of both water and lipid content is a requirement for spherical vesicles. In addition, the effect of these transmembrane proteins is studied in bilayers and vesicles, including investigations into hydrophobic matching and aggregation. Our simulations show that the level of aggregation does not only depend on hydrophobic mismatch, but also on protein shape. Additionally, one of the proteins promotes fusion by inducing pore formation. Incorporation of these proteins allows even flat membranes to fuse spontaneously. Moreover, we encountered a novel spontaneous vesicle enlargement mechanism we call the engulfing lobe, which may explain how lipids added to a vesicle solution are quickly incorporated into the inner monolayer.
细胞器之间的分子运输主要由囊泡的裂变和融合所控制。与实验囊泡不同，分子动力学模拟中的融合囊泡不易迅速变成球形，因为脂质和水的分布对于融合状态而言并不合适，且自发修正过程缓慢。在此，我们研究了这样一种假说，即需要增强水、脂质或两者跨膜的运输才能产生球形囊泡。这是通过向融合囊泡中添加几种模型蛋白来实现的。结果表明，水和脂质含量的平衡是形成球形囊泡的必要条件。此外，还在双层膜和囊泡中研究了这些跨膜蛋白的作用，包括对疏水匹配和聚集的研究。我们的模拟表明聚集程度不仅取决于疏水不匹配，还取决于蛋白质形状。此外，其中一种蛋白质通过诱导孔的形成来促进融合。这些蛋白质的掺入甚至能使扁平膜自发融合。此外，我们还遇到了一种新的自发囊泡扩大机制，我们称之为吞噬叶，这可能解释了添加到囊泡溶液中的脂质是如何迅速整合到内单层中的。
