Aggregation and hemi-fusion of anionic vesicles induced by the antimicrobial peptide cryptdin-4

被引:38
作者
Cummings, Jason E. [1 ]
Vanderlick, T. Kyle [1 ]
机构
[1] Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 2007年 / 1768卷 / 07期
基金
美国国家科学基金会;
关键词
peptide; aggregation; hemi-fusion; ctyptdin-4; defensin; vesicles;
D O I
10.1016/j.bbamem.2007.04.016
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We show that cryptdin-4 (Crp4), an antimicrobial peptide found in mice, induces the aggregation and hemi-fusion of charged phospholipid vesicles constructed of the anionic lipid POPG and the zwitterionic lipid POPC. Hemi-fusion is confirmed with positive total lipid-mixing assay results, negative inner monolayer lipid-mixing assay results, and negative results from contents-mixing assays. Aggregation, as quantified by absorbance and dynamic light scattering, is self-limiting, creating finite-sized vesicle assemblies. The rate limiting step in the formation process is the mixing of juxtaposed membrane leaflets, which is regulated by bound peptide concentration as well as vesicle radius (with larger vesicles less prone to hemi-fusion). Bound peptide concentration is readily controlled by total peptide concentration and the fraction of anionic lipid in the vesicles. As little as 1% PEGylated lipid significantly reduces aggregate size by providing a steric barrier for membrane apposition. Finally, as stable hemi-fusion is a rare occurrence, we compare properties of Crp4 to those of many peptides known to induce complete fusion and lend insight into conditions necessary for this unusual type of membrane merger. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:1796 / 1804
页数:9
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