基于R9抗菌肽与非对称磷脂膜的相互作用分析抗菌肽浓度对磷脂膜穿透的影响
Effects of Peptide Concentrations on Membrane Penetration from the Interaction of R9 Peptides with Asymmetric Lipid Bilayer
DOI: 10.12677/APP.2018.81003, PDF,  被引量    国家自然科学基金支持
作者: 吴 琦, 吴 坤, 孟庆田*：山东师范大学物理与电子科学学院，山东 济南
关键词: R9抗菌肽；非对称磷脂膜；粗粒化分子动力学模拟；R9 Peptide； Asymmetric Membrane； Coarse-Grained； Molecular Dynamics Simulation
摘要: 了解穿膜肽与细胞膜的相互作用在生物医学中具有重要意义。本文我们用粗粒化分子动力学模拟的方法研究了R9抗菌肽与非对称细胞膜之间的相互作用，发现单个抗菌肽自发穿透磷脂膜十分困难，只有当抗菌肽的浓度达到一个阈值，非对称膜形成一个亲水性的环形孔，随后抗菌肽沿此孔道穿过磷脂膜。这是由于抗菌肽协同效应及其与磷脂膜之间静电相互作用增强所致。随着抗菌肽浓度的增加，抗菌肽穿过的个数也随之增加。该研究能够帮助理解抗菌肽穿透细胞膜的机制，并对药物设计和药物传递有一定的意义。
Abstract: Understanding how cell-penetrating peptides interact with membrane is significant in biomedi-cine. In this article, we study the interactions between R9 peptides with asymmetric membranes by using coarse-grained molecular dynamics simulations. We find that it is very difficult for one peptide to cross over the lipid bilayer spontaneously. Only when the concentration of antibacterial peptide reaches a threshold can the asymmetric membrane form a hydrophilic circular pore, and the antibacterial peptide pass through the porous membrane along the pore channel, due to the synergistic effect of antimicrobial peptides and the enhancement of the electrostatic interaction between the antimicrobial peptides and the phospholipid membrane. With the increase of peptide concentration, the number of penetrating peptides also increases. Our research can better help to understand the mechanism of antimicrobial peptides penetrating the cell membrane and provide some help for the delivery of drugs.
文章引用：吴琦, 吴坤, 孟庆田. 基于R9抗菌肽与非对称磷脂膜的相互作用分析抗菌肽浓度对磷脂膜穿透的影响[J]. 应用物理, 2018, 8(1): 16-25. https://doi.org/10.12677/APP.2018.81003

参考文献

[1] Copolovici, D.M., Langel, K., Eriste, E., et al. (2014) Cell-Penetrating Peptides: Design, Synthesis, and Applications. ACS Nano, 8, 1972-1994. [Google Scholar] [CrossRef] [PubMed]
[2] Bechara, C. and Sagan, S. (2013) Cell-Penetrating Peptides: 20 Years Later, Where Do We Stand? FEBS Letters, 587, 1693-1702. [Google Scholar] [CrossRef] [PubMed]
[3] Bolhassani, A. (2011) Potential Efficacy of Cell-Penetrating Peptides for Nucleic Acid and Drug Delivery in Cancer. Biochimicaet Biophysica Acta (BBA)—Reviews on Cancer, 1816, 232-246. [Google Scholar] [CrossRef] [PubMed]
[4] Futaki, S. (2005) Membrane-Permeable Arginine-Rich Peptides and the Translocation Mechanisms. Advanced Drug Delivery Reviews, 57, 547-558. [Google Scholar] [CrossRef] [PubMed]
[5] Futaki, S., Nakase, I., Tadokoro, A., et al. (2007) Arginine-Rich Peptides and Their Internalization Mechanisms. Biochemical Society Transactions, 35, 784-787. [Google Scholar] [CrossRef] 
[6] Berlose, J.P., Convert, O., Derossi, D., et al. (1996) Conformational and Associative Behaviours of the Third Helix of Antennapedia Homeodomain in Membrane-Mimetic Environments. The FEBS Journal, 242, 372-386. [Google Scholar] [CrossRef] 
[7] Ding, H.M. and Ma, Y.Q. (2012) Role of Physicochemical Properties of Coating Ligands in Receptor-Mediated Endocytosis of Nanoparticles. Biomaterials, 33, 5798-5802. [Google Scholar] [CrossRef] [PubMed]
[8] Tian, W.D. and Ma, Y.Q. (2012) Insights into the Endosomal Escape Mechanism via Investigation of Dendrimer-Membrane Interactions. Soft Matter, 8, 6378-6384. [Google Scholar] [CrossRef] 
[9] Verkleij, A.J., Zwaal, R.F.A., Roelofsen, B., et al. (1973) The Asymmetric Distribution of Phospholipids in the Human Red Cell Membrane. A Combined Study Using Phospholipases and Freeze-Etch Electron Microscopy. BiochimicaetBiophysica Acta (BBA)—Biomembranes, 323, 178-193. [Google Scholar] [CrossRef] [PubMed]
[10] Sahu, S.K., Gummadi, S.N., Manoj, N., et al. (2007) Phospholipid Scramblases: An Overview. Archives of Biochemistry and Biophysics, 462, 103-114. [Google Scholar] [CrossRef] [PubMed]
[11] Li, Z.L., Ding, H.M. and Ma, Y.Q. (2012) Translocation of Polyarginines and Conjugated Nanoparticles across Asymmetric Membranes. Soft Matter, 9, 1281-1286. [Google Scholar] [CrossRef] 
[12] Ding, H.M. and Ma, Y.Q. (2015) Theoretical and Computational Investigations of Nanoparticle-Biomembrane Interactions in Cellular Delivery. Small, 11, 1055-1071. [Google Scholar] [CrossRef] [PubMed]
[13] Ding, H.M., Tian, W.D. and Ma, Y.Q. (2012) Designing Nanoparticle Translocation through Membranes by Computer Simulations. ACS Nano, 6, 1230-1238. [Google Scholar] [CrossRef] [PubMed]
[14] Yang, K. and Ma, Y.Q. (2010) Computer Simulation of the Translocation of Nanoparticles with Different Shapes across a Lipid Bilayer. Nature Nanotechnology, 5, 579-583. [Google Scholar] [CrossRef] [PubMed]
[15] Shi, X., Kong, Y. and Gao, H. (2008) Coarse Grained Molecular Dynamics and Theoretical Studies of Carbon Nanotubes Entering Cell Membrane. Acta Mechanica Sinica, 24, 161-169. [Google Scholar] [CrossRef] 
[16] Wang, J., Wei, Y., Shi, X., et al. (2013) Cellular Entry of Gra-phenenanosheets: The Role of Thickness, Oxidation and Surface Adsorption. RSC Advances, 3, 15776-15782. [Google Scholar] [CrossRef] 
[17] Marrink, S.J., Risselada, H.J., Yefimov, S., et al. (2007) The MARTINI Force Field: Coarse Grained Model for Biomolecular Simulations. The Journal of Physical Chemistry B, 111, 7812-7824. [Google Scholar] [CrossRef] [PubMed]
[18] Agrawal, P., Bhalla, S., Usmani, S.S., et al. (2016) CPPsite 2.0: A Repository of Experimentally Validated Cell-Penetrating Peptides. Nucleic Acids Research, 44, D1098-D1103. [Google Scholar] [CrossRef] [PubMed]
[19] Monticelli, L., Kandasamy, S.K., Periole, X., et al. (2008) The MARTINI Coarse-Grained Force Field: Extension to Proteins. Journal of Chemical Theory and Computation, 4, 819-834. [Google Scholar] [CrossRef] [PubMed]
[20] Takechi, Y., Yoshii, H., Tanaka, M., et al. (2011) Physicochemical Mechanism for the Enhanced Ability of Lipid Membrane Penetration of Polyarginine. Langmuir, 27, 7099-7107. [Google Scholar] [CrossRef] [PubMed]
[21] Marrink, S.J., De Vries, A.H. and Mark, A.E. (2004) Coarse Grained Model for Semiquantitative Lipid Simulations. The Journal of Physical Chemistry B, 108, 750-760. [Google Scholar] [CrossRef] 
[22] Wassenaar, T.A., Ingólfsson, H.I., Böckmann, R.A., et al. (2015) Computational Lipidomics with Insane: A Versatile Tool for Generating Custom Membranes for Molecular Simulations. Journal of Chemical Theory and Computation, 11, 2144-2155. [Google Scholar] [CrossRef] [PubMed]
[23] Lee, H. and Larson, R.G. (2006) Molecular Dynamics Simulations of PAMAM Dendrimer-Induced Pore Formation in DPPC Bilayers with a Coarse-Grained Model. The Journal of Physical Chemistry B, 110, 18204-18211. [Google Scholar] [CrossRef] [PubMed]
[24] Essmann, U., Perera, L., Berkowitz, M.L., et al. (1995) A Smooth Particle Mesh Ewald Method. The Journal of Chemical Physics, 103, 8577-8593. [Google Scholar] [CrossRef] 
[25] Li, Y., Chen, X. and Gu, N. (2008) Computational Investigation of Interaction between Nanoparticles and Membranes: Hydrophobic/Hydrophilic Effect. The Journal of Physical Chemistry B, 112, 16647-16653. [Google Scholar] [CrossRef] [PubMed]
[26] Van Der Spoel, D., Lindahl, E., Hess, B., et al. (2005) GROMACS: Fast, Flexible, and Free. Journal of Computational Chemistry, 26, 1701-1718. [Google Scholar] [CrossRef] [PubMed]
[27] Humphrey, W., Dalke, A. and Schulten, K. (1996) VMD: Visual Molecular Dynamics. Journal of Molecular Graphics, 14, 33-38. [Google Scholar] [CrossRef] [PubMed]
[28] He, X., Lin, M., Sha, B., et al. (2015) Coarse-Grained Molecular Dynamics Studies of the Translocation Mechanism of Polyarginines across Asymmetric Membrane under Tension. Scientific Reports, 5, Article No. 12808. [Google Scholar] [CrossRef] [PubMed]
[29] Su, Y., Waring, A.J., Ruchala, P., et al. (2010) Membrane-Bound Dynamic Structure of an Arginine-Rich Cell-Penetrating Peptide, the Protein Transduction Domain of HIV TAT, from Solid-State NMR. Biochemistry, 49, 6009-6020. [Google Scholar] [CrossRef] [PubMed]
[30] Lee, H. and Larson, R.G. (2008) Coarse-Grained Molecular Dynamics Studies of the Concentration and Size Dependence of Fifth- and Seventh-Generation PAMAM Dendrimers on Pore Formation in DMPC Bilayer. The Journal of Physical Chemistry B, 112, 7778-7784. [Google Scholar] [CrossRef] [PubMed]

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