Computer simulations of the interactions of high-generation polyamidoamine dendrimers with electronegative membranes
Computer simulations of the interactions of high-generation polyamidoamine dendrimers with electronegative membranes
复制标题
DOI：
10.1039/c3sm51572a
复制
发表时间：
2013-09
期刊：
影响因子：
3.4
通讯作者：
Li-qiang Xie;Wen-de Tian;Yu-qiang Ma
中科院分区：
文献类型：
--
作者：
Li-qiang Xie;Wen-de Tian;Yu-qiang Ma
采用粗粒化分子动力学模拟方法研究了第7、8和9代聚酰胺-胺树枝状大分子与两种带负电荷的双层膜的相互作用：一种是1，2-二肉豆蔻酰-sn-甘油-3-磷酸甘油（DMPG）和1，2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱（DMPC）以3：7的比例混合的双层膜，另一种是纯DMPG双层膜. 我们发现，在这两种情况下，高代树枝状大分子的配置只显示出非常轻微的变化。此外，随着混合双层逐渐包裹高代树枝状聚合物，由DMPG脂质组成的筏状结构域形成。另一方面，对于具有缺陷的纯DMPG双层，树枝状聚合物代越高，由于更强的静电吸引力，脂质从双层中去除得越快，并且预先存在的孔变得越大。此外，我们发现，在我们的模拟中的缺陷是负责形成一个树枝状聚合物包裹囊泡伴随着脂质翻转和树枝状聚合物旋转。囊泡的大小和脂质数被发现是在很好的协议与实验结果。我们建议，对于高代树枝状聚合物，这是可以接受的，脂质的去除机制与树枝状聚合物包裹囊泡模型解释。
Coarse-grained molecular dynamics simulations were performed to investigate the interactions of polyamidoamine dendrimers of generations 7, 8, and 9 with two types of negatively charged bilayers: one is a mixture of 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) in a ratio of 3 : 7, and the other is a pure DMPG bilayer. We find that in both cases the configuration of high-generation dendrimers only shows a very slight change. Furthermore, a raft-like domain composed of DMPG lipids forms as the mixed bilayer gradually wraps the high-generation dendrimers. On the other hand, for the pure DMPG bilayer with defects, the higher the dendrimer generation is, the faster the lipids are removed from the bilayer due to the stronger electrostatic attraction, and the larger the preexisted pore becomes. Moreover, we find that the defect in our simulations is responsible for the formation of a dendrimer-encased vesicle accompanied with the lipid flipping and dendrimer rotation. The size and lipid number of the vesicle are found to be in good agreement with experimental results. We suggest that for high-generation dendrimers, it is acceptable that the removal mechanism of lipids was interpreted with the dendrimer-encased vesicle model.