Department of Physical Chemistry 1, Lund University, SE-22100 Lund, Sweden.
LINXS Institute of Advanced Neutron and X-ray Science, Scheelevagen 19, 22370 Lund, Sweden.
Phys Chem Chem Phys. 2024 Jun 12;26(23):16529-16539. doi: 10.1039/d4cp01724b.
This study reports on the effects of conformationally controlled amphiphilicity of antimicrobial peptides (AMPs) on their ability to coat TiO nanoparticles (NPs) and boost the photocatalytic antimicrobial effects of such NPs. For this, TiO NPs were combined with AMP EFK17 (EKRVQRKDLRNLV), displaying a disordered conformation in aqueous solution but helix formation on interaction with bacterial membranes. The membrane-bound helix is amphiphilic, with all polar and charged amino acid residues located at one side and all non-polar and hydrophobic residues on the other. In contrast, the d-enantiomer variant EFK17-d (E(d)KR(d)VQR(d)KD(d)LRNLV) is unable to form the amphiphilic helix on bacterial membrane interaction, whereas the W-residues in EFK17-W (EKRVQRKDLRNLV) boost hydrophobic interactions of the amphiphilic helix. Circular dichroism results showed the effects displayed for the free peptide, to also be present for peptide-coated TiO NPs, causing peptide binding to decrease in the order EFK17-W > EFK17 > EFK17-d. Notably, the formation of reactive oxygen species (ROS) by the TiO NPs was essentially unaffected by the presence of peptide coating, for all the peptides investigated, and the coatings stabilized over hours of UV exposure. Photocatalytic membrane degradation from TiO NPs coated with EFK17-W and EFK17 was promoted for bacteria-like model bilayers containing anionic phosphatidylglycerol but suppressed in mammalian-like bilayers formed by zwitterionic phosphatidylcholine and cholesterol. Structural aspects of these effects were further investigated by neutron reflectometry with clear variations observed between the bacteria- and mammalian-like model bilayers for the three peptides. Mirroring these results in bacteria-like model membranes, combining TiO NPs with EFK17-W and EFK17, but not with non-adsorbing EFK17-d, resulted in boosted antimicrobial effects of the resulting cationic composite NPs already in darkness, effects enhanced further on UV illumination.
本研究报告了抗菌肽（AMPs）构象控制的两亲性对其将 TiO2纳米颗粒（NPs）涂层并增强此类 NPs 光催化抗菌效果的能力的影响。为此，将 TiO2NPs 与 AMP EFK17（EKRVQRKDLRNLV）结合，该 AMP 在水溶液中呈现无序构象，但与细菌膜相互作用时形成螺旋。结合膜的螺旋是两亲性的，所有极性和带电氨基酸残基位于一侧，所有非极性和疏水性残基位于另一侧。相比之下，E(d)KR(d)VQR(d)KD(d)LRNLV 不能在与细菌膜相互作用时形成两亲性螺旋，而 EFK17-W（EKRVQRKDLRNLV）中的 W 残基增强了两亲性螺旋的疏水相互作用。圆二色谱结果表明，游离肽显示的效果也存在于肽涂层的 TiO2NPs 中，导致肽结合按 EFK17-W>EFK17>EFK17-d 的顺序减少。值得注意的是，对于所有研究的肽，TiO2NPs 形成的活性氧物种（ROS）的形成基本上不受肽涂层的影响，并且涂层在数小时的 UV 暴露下稳定。用 EFK17-W 和 EFK17 涂覆的 TiO2NPs 促进了类似细菌的模型双层中阴离子磷脂酰甘油的膜降解，但在由两性离子磷脂酰胆碱和胆固醇形成的类似哺乳动物的双层中受到抑制。通过中子反射测量进一步研究了这些效应的结构方面，对于三种肽，在类似细菌和类似哺乳动物的模型双层之间观察到明显的变化。在类似细菌的模型膜中反映这些结果，将 TiO2NPs 与 EFK17-W 和 EFK17 结合，但与非吸附的 EFK17-d 结合，已经在黑暗中增强了所得阳离子复合 NPs 的抗菌效果，在 UV 照射下进一步增强。
