Membrane-active peptides that demonstrate cell-penetrating, antimicrobial or cytotoxic functions are diverse in their amino acid sequences, but share common physicochemical features like short length, amphipathic conformation in membrane environment and high net charge. Nonspecific electrostatic interactions of basic peptide residues with anionic membrane lipids play a crucial role in the initial binding of such peptides to plasma membranes of bacterial and mammalian cells. At the same time, a number of membrane-active peptides functions when they are localized at high concentrations on the lipid membranes. Dissecting the role of electrostatics in this functional peptide conditions is important to understand why the majority of them bear high positive charge. We have studied interaction of EB1 cell-penetrating peptide (charge + 8) with model anionic membranes. The saturation of peptide binding to liposomes that comprises 5%, 10% and 25% of negatively charged lipids (POPC/POPG mixture) was observed. We have found that peptide recharges liposomes and its surface saturating concentration increases with the amount of anionic lipids in a membrane so as a surface charge (bound peptide plus anionic lipids). This observation may be explained with the Gouy–Chapman theory based model with addition of independent effective peptide charges for peptide–peptide and peptide–lipid interactions, as well as steric saturation term. Additionally, in certain conditions, membrane bound peptide leads to liposome aggregation. In some lipid-to-peptide ratio regions disaggregation follows that may indicate an additional slow equilibration process after fast initial peptide binding.

具有细胞穿透、抗菌或细胞毒功能的膜活性肽的氨基酸序列多种多样，但具有共同的理化特征，如长度短、膜环境中的两亲构象和高净电荷。碱性肽残基与阴离子膜脂质的非特异性静电相互作用在此类肽与细菌和哺乳动物细胞质膜的初始结合中起着至关重要的作用。同时，许多膜活性肽在脂膜上以高浓度定位时发挥作用。剖析静电在这种功能性肽条件下的作用对于理解为什么大多数肽都带有高正电荷非常重要。我们研究了 EB1 细胞穿透肽（电荷 + 8）与模型阴离子膜的相互作用。观察到肽与包含5%、10%和25%带负电荷的脂质（POPC/POPG混合物）的脂质体结合的饱和度。我们发现肽对脂质体进行再充电，并且其表面饱和浓度随着膜中阴离子脂质的量而增加，因此作为表面电荷（结合的肽加上阴离子脂质）。这一观察结果可以用基于古伊-查普曼理论的模型来解释，该模型添加了肽-肽和肽-脂质相互作用的独立有效肽电荷以及空间饱和项。此外，在某些条件下，膜结合肽会导致脂质体聚集。在一些脂质与肽比率区域中，随后发生解聚，这可能表明在快速初始肽结合之后额外缓慢的平衡过程。