Single Vesicle Analysis Reveals Nanoscale Membrane Curvature Selective Pore Formation in Lipid Membranes by an Antiviral α-Helical Peptide

被引:55
作者
Tabaei, Seyed R. [2 ]
Rabe, Michael [2 ]
Zhdanov, Vladimir P. [2 ,3 ]
Cho, Nam-Joon [1 ]
Hook, Fredrik [2 ]
机构
[1] Nanyang Technol Univ, Sch Mat Sci & Engn, Singapore, Singapore
[2] Chalmers Univ Technol, Dept Appl Phys, S-41296 Gothenburg, Sweden
[3] Russian Acad Sci, Boreskov Inst Catalysis, Novosibirsk, Russia
基金
瑞典研究理事会; 英国医学研究理事会; 新加坡国家研究基金会;
关键词
Single molecule fluorescence microscopy; lipid vesicles; peptide nucleation; pore formation; membrane curvature; antiviral peptides; MECHANISM; KINETICS; BILAYER; LIPOSOMES; BINDING; LEAKAGE; CELL;
D O I
10.1021/nl3029637
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Using tethered sub-100 nm lipid vesicles that mimic enveloped viruses with nanoscale membrane curvature, we have in this Work designed a total internal reflection fluorescence microscopy-based single assay to investigate how an antiviral amphipathic alpha-helical (AH) peptide interacts with lipid membranes to induce membrane curvature-dependent. pore formation. and membrane destabilization. Based on a combination of statistics from single vesicle imaging, binding kinetics data, and theoretical analysis, we propose a mechanistic model that is consistent with the experimentally observed peptide association and pore formation kinetics at medically relevant peptide concentrations (10 nM to 1 mu M) and unusually low peptide-to-lipid (P/L), ratio (similar to 1/1000). Importantly, the preference of the AH peptide to selectively rupture virions with sub-100 nm diameters appears to be related to membrane strain-dependent pore formation rather than to previously observed nanoscale membrane. curvature facilitated binding of AH peptides. Compared to other known. proteins and peptides, the combination of low effective P/L ratio and high specificity for nm-sized membrane curvature lends this particular AH peptide great potential to serve as a framework for developing a highly specific and potent antiviral agent for prophylactic and therapeutic applications while avoiding toxic side effects against host cell membranes.
引用
收藏
页码:5719 / 5725
页数:7
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