Molecular mechanism of HIV-1 TAT peptide and its conjugated gold nanoparticles translocating across lipid membranes
Molecular mechanism of HIV-1 TAT peptide and its conjugated gold nanoparticles translocating across lipid membranes
复制标题
HIV-1 TAT肽及其缀合金纳米粒子跨脂膜易位的分子机制
DOI：
10.1039/c9cp01543d
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发表时间：
2019-05-28
影响因子：
3.3
通讯作者：
Zhou, Jian
中科院分区：
文献类型：
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作者：
Quan, Xuebo;Sun, Delin;Zhou, Jian
来自人类免疫缺陷病毒-1（human immunodeficiency virus-1，HIV-1）的反式转录激活因子（trans-acting activator of transcription，达特）肽作为一种有效的纳米载体被广泛应用于细胞外物质的转运。然而，达特肽跨膜转运的机制仍然存在争议。此外，达特肽促进细胞外物质转运到细胞内的分子过程在很大程度上是未知的。在这项研究中，我们探索达特肽和它们的共轭金纳米粒子与脂质膜的相互作用，粗粒度的分子动力学模拟。发现达特肽在低肽浓度下几乎不能穿透膜;在浓度增加到阈值后，由于跨膜静电势差，它们可以通过诱导的纳米孔穿过膜。达特肽的移位主要是由膜的整体结构变化引起的。此外，我们证明了金纳米颗粒（AuNPs）跨膜的易位受到颗粒表面上接枝的达特肽的数量的显着影响。当少量肽修饰它们时，AuNP的跨膜效率甚至可能降低;然而，当接枝肽的数量增加到一定值时，TAT-AuNP复合物可以以孔介导的方式跨膜易位。基于我们的研究结果，提出了一种有效的策略，以提高金纳米粒子的交付效率。本研究有助于加深对达特肽与细胞膜相互作用的理解，并为设计和开发高效的纳米载体提供一些有意义的建议。
The trans-acting activator of transcription (TAT) peptide, which is derived from human immunodeficiency virus-1 (HIV-1), has been widely used as an effective nanocarrier to transport extracellular substances into cells. However, the underlying translocation mechanism of TAT peptide across cell membranes still remains controversial. Besides, the molecular process of TAT peptide facilitating the transport of extracellular substances into cells is largely unknown. In this study, we explore the interactions of TAT peptides and their conjugated gold nanoparticles with lipid membranes by coarse-grained molecular dynamics simulations. It is found that the TAT peptides can hardly penetrate through the membrane at low peptide concentrations; after the concentration increases to a threshold value, they can cross the membrane through an induced nanopore due to the transmembrane electrostatic potential difference. The translocation of TAT peptides is mainly caused by the overall structural changes of membranes. Furthermore, we demonstrate that the translocation of gold nanoparticles (AuNPs) across the membrane is significantly affected by the number of grafted TAT peptides on the particle surface. The transmembrane efficiency of AuNPs may even be reduced when a small number of peptides modify them; whereas, when the number of grafted peptides increases to a certain value, the TAT-AuNP complex can translocate across the membrane in a pore-mediated way. Based on our findings, an effective strategy has been proposed to enhance the delivery efficiency of AuNPs. The present study can improve our understanding of the interactions between TAT peptides and cell membranes; it may also give some insightful suggestions on the design and development of nanocarriers with high efficiency for the delivery of nanoparticles and drugs.