Zan Goh Haw, Jackman Joshua A, Cho Nam-Joon
School of Materials Science and Engineering, Nanyang Technological University , 50 Nanyang Avenue 639798, Singapore.
J Phys Chem B. 2014 Apr 3;118(13):3616-21. doi: 10.1021/jp411648s. Epub 2014 Mar 25.
Planar lipid bilayers on solid supports provide a controllable platform to mimic biological membranes. Adsorption and spontaneous rupture of vesicles is the most common method to form planar bilayers. While many substrates support vesicle adsorption, vesicles rupture spontaneously on only a few materials. In order to form planar bilayers on materials intractable to conventional vesicle fusion, an amphipathic, α-helical (AH) peptide has been identified that can rupture adsorbed vesicles and form planar bilayers on previously intractable materials. Most studies using AH peptide have employed zwitterionic lipid compositions only, and the range of suitable lipid compositions remains to be elucidated. Herein, using quartz crystal microbalance-dissipation and ellipsometry, we investigated the effects of membrane surface charge on AH peptide-mediated bilayer formation via the rupture of surface-adsorbed vesicles on titanium oxide. Our findings demonstrate that AH peptide can promote the formation of positively and negatively charged bilayers. Importantly, the kinetics of vesicle rupture by AH peptide are strongly influenced by the membrane surface charge. Although the titanium oxide surface is negatively charged, the formation of negatively charged bilayers was quickest among the tested lipid compositions. Taken together, the experimental data supports that the effects of membrane surface charge on the rupture kinetics are related to variations in the extent of vesicle destabilization prior to vesicle rupture. Given the wide range of lipid compositions amenable to AH peptide-mediated vesicle rupture, this work further suggests that AH peptide is largely unique among membrane-active peptides, thereby substantiating its position as a promising broad-spectrum antiviral agent.
固体支持物上的平面脂质双层为模拟生物膜提供了一个可控的平台。囊泡的吸附和自发破裂是形成平面双层的最常见方法。虽然许多底物支持囊泡吸附，但囊泡仅在少数材料上自发破裂。为了在传统囊泡融合难以处理的材料上形成平面双层，已鉴定出一种两亲性α-螺旋（AH）肽，它可以使吸附的囊泡破裂并在以前难以处理的材料上形成平面双层。大多数使用AH肽的研究仅采用两性离子脂质组合物，合适的脂质组合物范围仍有待阐明。在此，我们使用石英晶体微天平耗散技术和椭偏仪，研究了膜表面电荷对AH肽介导的双层形成的影响，该双层形成是通过氧化钛表面吸附的囊泡破裂实现的。我们的研究结果表明，AH肽可以促进带正电和带负电双层的形成。重要的是，AH肽导致囊泡破裂的动力学受到膜表面电荷的强烈影响。尽管氧化钛表面带负电，但在测试的脂质组合物中，带负电双层的形成最快。综上所述，实验数据支持膜表面电荷对破裂动力学的影响与囊泡破裂前囊泡不稳定程度的变化有关。鉴于AH肽介导的囊泡破裂适用于广泛的脂质组合物，这项工作进一步表明，AH肽在膜活性肽中在很大程度上是独特的，从而证实了其作为一种有前途的广谱抗病毒剂的地位。
