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阳离子脂质诱导 DNA 凝聚的机制：脂质-DNA 配位和二价阳离子电荷波动。

Mechanism of Cationic Lipid Induced DNA Condensation: Lipid-DNA Coordination and Divalent Cation Charge Fluctuations.

机构信息

Chemistry Program, Science Division, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.

Department of Chemistry, New York University, New York, New York 10003, United States.

出版信息

Biomacromolecules. 2024 Aug 12;25(8):4819-4830. doi: 10.1021/acs.biomac.4c00192. Epub 2024 Jul 16.

DOI:10.1021/acs.biomac.4c00192
PMID:39011747
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11323003/
Abstract

The condensation of nucleic acids by lipids is a widespread phenomenon in biology with crucial implications for drug delivery. However, the mechanisms of DNA assembly in lipid bilayers remain insufficiently understood due to challenges in measuring and assessing each component's contribution in the lipid-DNA-cation system. This study uses all-atom molecular dynamics simulations to investigate DNA condensation in cationic lipid bilayers. Our exhaustive exploration of the thermodynamic factors reveals unique roles for phospholipid head groups and cations. We observed that bridging cations between lipid and DNA drastically reduce charges, while mobile magnesium cations "ping-ponging" between double strands create charge fluctuations. While the first factor stabilizes the DNA-lipid complex, the latter creates attractive forces to induce the spontaneous condensation of DNAs. This novel mechanism not only sheds light on the current data regarding cationic lipid-induced DNA condensation but also provides potential design strategies for creating efficient gene delivery vectors for drug delivery.

摘要

脂质使核酸发生凝聚是生物学中的一种普遍现象，对药物输送具有重要意义。然而，由于难以测量和评估脂质-DNA-阳离子系统中每个成分的贡献，因此对于 DNA 在脂质双层中的组装机制仍了解不足。本研究使用全原子分子动力学模拟来研究阳离子脂质双层中的 DNA 凝聚。我们详尽地研究了热力学因素，揭示了磷脂头部基团和阳离子的独特作用。我们观察到，脂质和 DNA 之间的桥连阳离子极大地降低了电荷，而在双链之间“乒乓”运动的可移动镁阳离子则产生了电荷波动。虽然第一个因素稳定了 DNA-脂质复合物，但后者则产生了吸引力，从而诱导 DNA 的自发凝聚。这种新的机制不仅阐明了当前关于阳离子脂质诱导 DNA 凝聚的实验数据，而且为设计高效的基因传递载体提供了潜在的策略，以用于药物输送。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/176cf457ef8b/bm4c00192_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/ee8a20bc216e/bm4c00192_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/9c89e3672842/bm4c00192_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/7dd4f4cc9d0c/bm4c00192_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/0f6f5956a2d2/bm4c00192_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/12ec89875b8b/bm4c00192_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/a43a53879937/bm4c00192_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/176cf457ef8b/bm4c00192_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/ee8a20bc216e/bm4c00192_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/9c89e3672842/bm4c00192_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/7dd4f4cc9d0c/bm4c00192_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/0f6f5956a2d2/bm4c00192_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/12ec89875b8b/bm4c00192_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/a43a53879937/bm4c00192_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/11323003/176cf457ef8b/bm4c00192_0007.jpg

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本文引用的文献

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