Juhaniewicz-Debinska Joanna
Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, ul. Zwirki i Wigury 101, 02-089 Warsaw, Poland.
Molecules. 2024 Dec 23;29(24):6064. doi: 10.3390/molecules29246064.
In this study, we explore the interactions between melittin, a cationic antimicrobial peptide, and model lipid membranes composed of the negatively charged phospholipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) and 1,2-dimyristoyl-sn-glycero-3-phosphoserine (DMPS). Using the Langmuir monolayer technique and atomic force microscopy (AFM), we reveal novel insights into these interactions. Our key finding is the observation of the ripple phase in the DMPS bilayer on mica, a phenomenon not previously reported for negatively charged single bilayers. This discovery is significant given the critical role of phosphatidylserine (PS) in cancer biology and the potential of melittin as an anticancer agent. We also highlight the importance of subphase composition, as melittin interacts preferentially with lipids in the liquid-condensed phase; thus, selecting the appropriate subphase composition is crucial because it affects lipid behavior and consequently melittin interactions. Our results show that melittin incorporates into lipid monolayers in both liquid-expanded and liquid-condensed phases, enhancing membrane fluidity and disorder, but is expelled from DMPS in the solid phase. AFM imaging further reveals that melittin induces substantial structural changes in the DMPG membrane and forms the ripple phase in the DMPS bilayers. Despite these alterations, melittin does not cause pore formation or membrane rupture, suggesting strong electrostatic adsorption on the membrane surface that prevents penetration. These findings highlight the differential impacts of melittin on lipid monolayers and bilayers and underscore its potential for interacting with membranes without causing disruption.
在本研究中，我们探究了阳离子抗菌肽蜂毒肽与由带负电荷的磷脂1,2-二肉豆蔻酰-sn-甘油-3-磷酸甘油（DMPG）和1,2-二肉豆蔻酰-sn-甘油-3-磷酸丝氨酸（DMPS）组成的模型脂质膜之间的相互作用。利用Langmuir单分子层技术和原子力显微镜（AFM），我们揭示了这些相互作用的新见解。我们的关键发现是观察到云母上DMPS双层中的波纹相，这一现象此前在带负电荷的单双层中未见报道。鉴于磷脂酰丝氨酸（PS）在癌症生物学中的关键作用以及蜂毒肽作为抗癌剂的潜力，这一发现具有重要意义。我们还强调了亚相组成的重要性，因为蜂毒肽优先与液晶相中的脂质相互作用；因此，选择合适的亚相组成至关重要，因为它会影响脂质行为，进而影响蜂毒肽的相互作用。我们的结果表明，蜂毒肽在液晶态和液态扩展相中都能融入脂质单分子层，增强膜的流动性和无序性，但在固态时会从DMPS中被排出。AFM成像进一步揭示，蜂毒肽会在DMPG膜中引起显著的结构变化，并在DMPS双层中形成波纹相。尽管有这些改变，蜂毒肽不会导致孔形成或膜破裂，这表明它在膜表面有强烈的静电吸附，从而阻止其穿透。这些发现突出了蜂毒肽对脂质单分子层和双层的不同影响，并强调了其与膜相互作用而不造成破坏的潜力。
