Polybia-MP1 or simply MP1 (IDWKKLLDAAKQIL-NH2) is a peptide with broad-spectrum bactericidal activity and a strong inhibitory effect against cancer cells. The aim of this work was to evaluate the effect of biophysical properties such as membrane texture and film thickness on MP1 interaction with neutral and anionic lipid membranes. For this purpose, we first explored the peptide's surface behavior. MP1 showed high surface activity, adsorbing onto bare air/aqueous interfaces up to higher surface pressures than the collapse pressure of MP1 Langmuir films. The MP1-lipid membrane interaction was studied using Langmuir phosphatidylcholine and phosphatidylserine (PS) monolayers as model membrane systems. PS was chosen since this negatively charged lipid was found predominantly on the outer leaflet of tumor cells, and it enhances MP1 activity for PS-containing membranes to a greater extent than for other negatively charged lipids. MP1 incorporated into anionic PS monolayers, which show a liquid-expanded (LE) phase or LE-liquid-condensed (LC) phase coexistence, up to lipid-packing densities higher than those of cell membranes. The mixed lipid/MP1 films were explored by Brewster angle microscopy and atomic force microscopy. MP1 partitioned preferentially into the LE phase state of PS films, and were thus excluded from the coexisting LC phase. This interaction had strong electrostatic bases: in pure water, the lipid-peptide interaction was strong enough to induce formation of reversible lipid-peptide 3D structures associated with the interface. MP1 incorporation into the LE phase was accompanied by a shift of the phase transition pressure to higher values and a thinning of the lipid film. These results showed a clear correlation between peptide penetration capacity and the presence or induction of the thin LE phase. This capacity to regulate membrane physical properties may be of relevance in the binding, incorporation and membrane selectivity of this promising antitumor peptide.

中文翻译：

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Polybia-MP1肽插入磷脂单层的过程受其阴离子性质和相态的调节。

Polybia-MP1或简称MP1（IDWKKLLDAAKQIL-NH2）是一种具有广谱杀菌活性且对癌细胞具有强抑制作用的肽。这项工作的目的是评估生物物理特性（例如膜质地和膜厚度）对MP1与中性和阴离子脂质膜相互作用的影响。为此，我们首先探讨了该肽的表面行为。MP1具有较高的表面活性，可吸附到空气/水界面上，其表面压力比MP1 Langmuir膜的破裂压力高。使用Langmuir磷脂酰胆碱和磷脂酰丝氨酸（PS）单层作为模型膜系统研究了MP1-脂质膜的相互作用。选择PS是因为这种带负电荷的脂质主要存在于肿瘤细胞的外部小叶上，与其他带负电荷的脂质相比，它可以更大程度地提高含PS膜的MP1活性。包含在阴离子PS单层中的MP1，它们表现出液胀（LE）相或LE液凝（LC）相共存，直至脂质堆积密度高于细胞膜。通过布鲁斯特角显微镜和原子力显微镜探索混合的脂质/ MP1膜。MP1优先划分为PS膜的LE相状态，因此从共存的LC相中排除。这种相互作用具有很强的静电基础：在纯水中，脂质-肽之间的相互作用足以诱导与界面相关的可逆脂质-肽3D结构的形成。将MP1掺入LE相的过程中，伴随着相变压力向更高值的转移以及脂质膜的变薄。这些结果表明肽渗透能力与稀LE相的存在或诱导之间存在明显的相关性。调节膜物理性质的能力可能与这种有希望的抗肿瘤肽的结合，掺入和膜选择性有关。