Department of Chemistry, University of Oslo, 0315 Oslo, Norway.
Biofilms Research Center for Biointerfaces, Department of Biomedical Science, Health and Society, Malmö University, 20506 Malmö, Sweden.
Biochim Biophys Acta Biomembr. 2019 Jul 1;1861(7):1355-1364. doi: 10.1016/j.bbamem.2019.04.003. Epub 2019 Apr 9.
The naturally occurring peptide indolicidin from bovine neutrophils exhibits strong biological activity against a broad spectrum of microorganisms. This is believed to arise from selective interactions with the negatively charged cytoplasmic lipid membrane found in bacteria. We have investigated the peptide interaction with supported lipid model membranes using a combination of complementary surface sensitive techniques: neutron reflectometry (NR), atomic force microscopy (AFM), and quartz crystal microbalance with dissipation monitoring (QCM-D). The data are compared with small-angle X-ray scattering (SAXS) results obtained with lipid vesicle/peptide solutions. The peptide membrane interaction is shown to be significantly concentration dependent. At low concentrations, the peptide inserts at the outer leaflet in the interface between the headgroup and tail core. Insertion of the peptide results in a slight decrease in the lipid packing order of the bilayer, although not sufficient to cause membrane thinning. By increasing the indolicidin concentration well above the physiologically relevant conditions, a deeper penetration of the peptide into the bilayer and subsequent lipid removal take place, resulting in a slight membrane thinning. The results suggest that indolicidin induces lipid removal and that mixed indolicidin-lipid patches form on top of the supported lipid bilayers. Based on the work presented using model membranes, indolicidin seems to act through the interfacial activity model rather than through the formation of stable pores.
牛中性粒细胞来源的天然肽抑菌素对广谱微生物具有很强的生物活性。这被认为是由于与细菌中带负电荷的细胞质脂膜的选择性相互作用所致。我们使用一系列互补的表面敏感技术：中子反射（NR）、原子力显微镜（AFM）和石英晶体微天平耗散监测（QCM-D），研究了肽与支撑脂质模型膜的相互作用。将数据与脂质囊泡/肽溶液的小角度 X 射线散射（SAXS）结果进行了比较。结果表明，肽与膜的相互作用显著依赖于浓度。在低浓度下，肽插入到头部基团和尾部核心之间的界面的外层。肽的插入导致双层脂质堆积顺序略有下降，尽管不足以导致膜变薄。通过将抑菌素的浓度提高到远高于生理相关的条件，肽更深地插入双层膜，随后脂质被去除，导致膜略微变薄。结果表明，抑菌素诱导脂质去除，并且混合的抑菌素-脂质斑在支撑脂质双层的顶部形成。基于使用模型膜进行的工作，抑菌素似乎通过界面活性模型起作用，而不是通过形成稳定的孔起作用。
