Kelley Elizabeth G, Butler Paul D, Nagao Michihiro
NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD, USA.
Soft Matter. 2021 Jun 16;17(23):5671-5681. doi: 10.1039/d1sm00314c.
Biological membranes are composed of complex mixtures of lipids and proteins that influence each other's structure and function. The biological activities of many channel-forming peptides and proteins are known to depend on the material properties of the surrounding lipid bilayer. However, less is known about how membrane-spanning channels affect the lipid bilayer properties, and in particular, their collective fluctuation dynamics. Here we use neutron spin echo spectroscopy (NSE) to measure the collective bending and thickness fluctuation dynamics in dimyristoylphosphatidylcholine (di 14 : 0 PC, DMPC) lipid membranes containing two different antimicrobial peptides, alamethicin (Ala) and gramicidin (gD). Ala and gD are both well-studied antimicrobial peptides that form oligomeric membrane-spanning channels with different structures. At low concentrations, the peptides did not have a measurable effect on the average bilayer structure, yet significantly changed the collective membrane dynamics. Despite both peptides forming transmembrane channels, they had opposite effects on the relaxation time of the collective bending fluctuations and associated effective bending modulus, where gD addition stiffened the membrane while Ala addition softened the membrane. Meanwhile, the lowest gD concentrations enhanced the collective thickness fluctuation dynamics, while the higher gD concentrations and all studied Ala concentrations dampened these dynamics. The results highlight the synergy between lipids and proteins in determining the collective membrane dynamics and that not all peptides can be universally treated as rigid bodies when considering their effects on the lipid bilayer fluctuations.
生物膜由脂质和蛋白质的复杂混合物组成,这些成分相互影响彼此的结构和功能。已知许多形成通道的肽和蛋白质的生物活性取决于周围脂质双层的材料特性。然而,关于跨膜通道如何影响脂质双层特性,尤其是其集体波动动力学,人们了解得较少。在这里,我们使用中子自旋回波光谱(NSE)来测量含有两种不同抗菌肽(短杆菌肽A(Ala)和短杆菌肽(gD))的二肉豆蔻酰磷脂酰胆碱(di 14 : 0 PC,DMPC)脂质膜中的集体弯曲和厚度波动动力学。Ala和gD都是经过充分研究的抗菌肽,它们形成具有不同结构的寡聚跨膜通道。在低浓度下,这些肽对平均双层结构没有可测量的影响,但显著改变了集体膜动力学。尽管两种肽都形成跨膜通道,但它们对集体弯曲波动的弛豫时间和相关的有效弯曲模量有相反的影响,添加gD使膜变硬,而添加Ala使膜变软。同时,最低浓度的gD增强了集体厚度波动动力学,而较高浓度的gD和所有研究的Ala浓度则抑制了这些动力学。结果突出了脂质和蛋白质在决定集体膜动力学方面的协同作用,并且在考虑它们对脂质双层波动的影响时,并非所有肽都可以被普遍视为刚体。