Computational investigations of a Peptide-modified dendrimer interacting with lipid membranes.
Computational investigations of a Peptide-modified dendrimer interacting with lipid membranes.
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DOI：
10.1002/marc.201300360
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发表时间：
2013-08
影响因子：
4.6
通讯作者：
Chen-kun Tu;Kang Chen;Wen-de Tian;Yu-qiang Ma
中科院分区：
文献类型：
--
作者：
Chen-kun Tu;Kang Chen;Wen-de Tian;Yu-qiang Ma
了解树状大分子作为传递载体与生物膜的相互作用对功能优化非常重要。本文采用粗粒度的分子动力学模拟研究了生理和低pH条件下具有短肽的表面修饰树状大分子与脂质双分子层之间的相互作用。该肽由三个具有ph敏感性的组氨酸(H)和一个精氨酸(R)组成。研究发现，肽-树状大分子缀合物粘附或穿透带负电荷的不对称双分子层，这取决于pH值。平均力势的计算表明，在低ph下，渗透是有利于能量的。共轭物可以使膜变薄，同时增强渗透性。受此结果的启发，我们提出了一种利用pH环境调节的非特异性静电相互作用来传递基因的可能途径。
Understanding the interactions of dendrimers as delivery vectors with biomembranes is important for functional optimization. Here, coarse-grained molecular dynamics simulations are employed to study the interactions between a surface-modified dendrimer with short peptides and lipid bilayers under physiological and low pH conditions. The peptide consists of three histidines (H) with the pH-sensitive property and an arginine (R). It is found that the peptide-dendrimer conjugate either adheres to or penetrates through the negatively charged, asymmetrical bilayer, dependent on the pH value. Calculation of the potential of mean force shows that the penetration is energy favorable at low pH. The conjugate can lead to membrane thinning with enhanced permeability. Inspired by the results, a possible route is proposed for gene delivery using the non-specific electrostatic interaction adjusted by the pH environment.