Department of Chemistry, University of Oslo, 0315 Oslo, Norway.
Institut Laue - Langevin, 38000 Grenoble, France.
Faraday Discuss. 2021 Dec 24;232(0):203-217. doi: 10.1039/d0fd00046a.
The mechanism of action of antimicrobial peptides (AMPs) has been debated over many years, and various models have been proposed. In this work we combine small angle X-ray/neutron scattering (SAXS/SANS) techniques to systematically study the effect of AMPs on the cytoplasmic membrane of bacteria using a simplified model system of 4 : 1 DMPE : DMPG ([1,2-dimyristoyl--3-phosphoethanolamine] : [1,2-dimyristoyl--3-phospho-(10--glycerol)]) phospholipid unilamellar vesicles. The studied antimicrobial peptides aurein 1.2, indolicidin, LL-37, lacticin Q and colistin vary in size, charge, degree of helicity and origin. The peptides insert into the bilayer to various degrees, and are found to accelerate the dynamics of phospholipids significantly as seen by time resolved SANS (TR-SANS) measurements, with the exception of colistin that is suggested to rather interact with lipopolysaccharides (LPS) on the outer membrane of . We compare these results with earlier published data on model systems based on PC-lipids (phosphatidylcholines), showing comparable effect with regards to peptide insertion and effect on dynamics. However, model systems based on PE-lipids (phosphatidylethanolamine) are more prone to destabilisation upon addition of peptides, with formation of multilamellar structures and morphological changes. These properties of PE-vesicles lead to less conclusive results regarding peptide effect on structure and dynamics of the membrane.
抗菌肽（AMPs）的作用机制多年来一直存在争议，提出了各种模型。在这项工作中，我们结合小角 X 射线/中子散射（SAXS/SANS）技术，使用 4∶1 DMPE∶DMPG（[1,2-二肉豆蔻酰基-3-磷酸乙醇胺]∶[1,2-二肉豆蔻酰基-3-磷酸-(10-甘油)]）磷脂单层囊泡的简化模型系统，系统地研究了 AMP 对细菌细胞质膜的影响。研究的抗菌肽 aurein 1.2、indolicidin、LL-37、lacticin Q 和 colistin 在大小、电荷、螺旋度和来源上有所不同。这些肽以不同程度插入双层，并且如通过时间分辨小角中子散射（TR-SANS）测量所看到的，显著加速了磷脂的动力学，除了 colistin 之外，colistin 被认为与其外膜上的脂多糖（LPS）相互作用。我们将这些结果与基于 PC-脂质（磷脂酰胆碱）的模型系统的早期发表数据进行了比较，显示出关于肽插入和对动力学的影响的可比效果。然而，基于 PE-脂质（磷脂酰乙醇胺）的模型系统在添加肽时更容易失稳，形成多层结构和形态变化。PE-囊泡的这些特性导致关于肽对膜结构和动力学的影响的结果不太确定。
