蜂毒肽与多组分生物膜作用:电性与相态的影响

Interaction between melittin and multicomponent biomembranes:effects of electrical and phase properties

蜂毒非特异性的靶向杀伤细菌具有重要的生物医学应用前景.利用荧光光谱与荧光显微考察了蜂毒肽与单组分、多组分磷脂膜的作用机制.发现对于不同电性与相态的磷脂膜,肽-膜作用呈现为稳定桶板型孔、非稳U型孔及变薄裂解等多种机制,具有显著不同的内含物泄露效率.多组分磷脂囊泡的泄露实验表明,泄露由肽亲和性较强的磷脂组分决定.相较于凝胶相磷脂,蜂毒肽与液相磷脂的亲和性强,凝胶-液相混合囊泡与纯液相磷脂囊泡的泄露性质相近;相较于双电性磷脂,蜂毒肽与负电性磷脂的亲和性强,双电-负电混合囊泡与纯负电磷脂囊泡的泄露性质相近.研究深化了多肽与多组分生物膜作用机制的理解.

Antimicrobial peptides are the natural immunity tools against bacteria in animals with high biomedical research value. Melittin is a typical cationic amphiphilic antimicrobial peptide, which can nonspecifically target bacteria and cause bacterial death. In order to understand the targeted killing mechanism of melittin, it is necessary to understand the interactions between melittin and various biomembranes. In this research, we investigated the interaction mechanisms between melittin and mono-component and multi-component phospholipid model membranes using fluorescence spectroscopy method. The mono-component vesicle experiments showed that the mechanisms of melittin acting on biomembranes with various phase and electrical properties are significantly different. Many barrel-stave holes form in the zwitterionic liquid membranes and the leakage is efficient. Only a few unstable U-shaped pores form in zwitterionic gel membranes and the leakage rate is lower. And two interaction stages were observed in the negatively charged membranes, i.e. parallel peptide binding and membrane thinning-cleavage, and the leakage rate is the lowest. Additionally, for the multi-component membranes, the leakage is determined by the lipids showing strong affinity to the peptides. In the liquid-gel mixtures, the affinity between liquid phospholipids and peptides is strong. Therefore, the leakage property of liquid-gel mixtures is similar to that of the pure liquid. And the leakage properties of negatively-neutrally charged lipid mixtures are similar to those of the pure negatively charged lipid membranes, because the latters display stronger affinity to melittins. This study deepens the understanding of the interactions between peptides and biomembranes. And it provides a reference for the peptide-related controlled release durg-delivery systems.