Sharma V K, Mamontov E, Tyagi M, Qian S, Rai D K, Urban V S
Biology and Soft Matter Division, Neutron Sciences Directorate, Oak Ridge National Laboratory , Oak Ridge, Tennessee 37831, United States.
Solid State Physics Division, Bhabha Atomic Research Centre , Mumbai 400085, India.
J Phys Chem Lett. 2016 Jul 7;7(13):2394-401. doi: 10.1021/acs.jpclett.6b01006. Epub 2016 Jun 15.
The mechanism of action of antimicrobial peptides is traditionally attributed to the formation of pores in the lipid cell membranes of pathogens, which requires a substantial peptide to lipid ratio. However, using incoherent neutron scattering, we show that even at a concentration too low for pore formation, an archetypal antimicrobial peptide, melittin, disrupts the regular phase behavior of the microscopic dynamics in a phospholipid membrane, dimyristoylphosphatidylcholine (DMPC). At the same time, another antimicrobial peptide, alamethicin, does not exert a similar effect on the DMPC microscopic dynamics. The melittin-altered lateral motion of DMPC at physiological temperature no longer resembles the fluid-phase behavior characteristic of functional membranes of the living cells. The disruptive effect demonstrated by melittin even at low concentrations reveals a new mechanism of antimicrobial action relevant in more realistic scenarios, when peptide concentration is not as high as would be required for pore formation, which may facilitate treatment with antimicrobial peptides.
传统上认为抗菌肽的作用机制是在病原体的脂质细胞膜上形成孔道，这需要相当高的肽与脂质比例。然而，通过非相干中子散射，我们发现即使在浓度低至无法形成孔道的情况下，一种典型的抗菌肽——蜂毒肽，也会破坏磷脂膜二肉豆蔻酰磷脂酰胆碱（DMPC）中微观动力学的正常相行为。同时，另一种抗菌肽——阿拉霉素，对DMPC的微观动力学没有类似影响。在生理温度下，蜂毒肽改变的DMPC横向运动不再类似于活细胞功能膜的液相行为特征。蜂毒肽即使在低浓度下也表现出的破坏作用揭示了一种在更实际情况下相关的新抗菌作用机制，即当肽浓度不像形成孔道所需的那么高时，这可能有助于抗菌肽的治疗。
