Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States.
J Phys Chem Lett. 2023 Jun 29;14(25):5841-5849. doi: 10.1021/acs.jpclett.3c00725. Epub 2023 Jun 20.
Cationic membrane-permeating peptides can cross membranes unassisted by transmembrane protein machinery, and there is consensus that anionic lipids facilitate this process. Although membranes are asymmetric in lipid composition, investigations of the impact of anionic lipids on peptide-membrane insertion in model vesicles primarily use symmetric anionic lipid distributions between bilayer leaflets. Here, we investigate the leaflet-specific influence of three anionic lipid headgroups [phosphatidic acid (PA), phosphatidylserine (PS), and phosphatidylglycerol (PG)] on insertion into model membranes by three cationic membrane-permeating peptides (NAF-1, RW, and WWWK). We report that outer leaflet anionic lipids enhanced peptide-membrane insertion for all peptides while inner leaflet anionic lipids did not have a significant effect except in the case of NAF-1 incubated with PA-containing vesicles. The insertion enhancement was headgroup-dependent for arginine-containing peptides but not WWWK. These results provide significant new insight into the potential role of membrane asymmetry in insertion of peptides into model membranes.
阳离子膜渗透肽可以在没有跨膜蛋白机制的帮助下穿过膜，人们普遍认为阴离子脂质有助于这一过程。尽管膜在脂质组成上是不对称的，但在模型囊泡中研究阴离子脂质对肽-膜插入的影响主要使用双层叶间的对称阴离子脂质分布。在这里，我们通过三种阳离子膜渗透肽（NAF-1、RW 和 WWWK）研究了三种阴离子脂质头基[磷脂酸 (PA)、磷脂酰丝氨酸 (PS) 和磷脂酰甘油 (PG)]对插入模型膜的叶特异性影响。我们报告说，所有肽的外层阴离子脂质都增强了肽-膜插入，而内层阴离子脂质除了与含有 PA 的囊泡孵育的 NAF-1 外，没有显著影响。对于含有精氨酸的肽，插入增强与头基有关，但 WWWK 则不是。这些结果为膜不对称性在肽插入模型膜中的潜在作用提供了重要的新见解。
