Institute of Biochemistry, Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania.
Molecules. 2021 Nov 15;26(22):6878. doi: 10.3390/molecules26226878.
Tethered bilayer lipid membranes (tBLMs) have been known as stable and versatile experimental platforms for protein-membrane interaction studies. In this work, the assembly of functional tBLMs on silver substrates and the effect of the molecular chain-length of backfiller molecules on their properties were investigated. The following backfillers 3-mercapto-1-propanol (3M1P), 4-mercapto-1-butanol (4M1B), 6-mercapto-1-hexanol (6M1H), and 9-mercapto-1-nonanol (9M1N) mixed with the molecular anchor WC14 (20-tetradecyloxy-3,6,9,12,15,18,22 heptaoxahexatricontane-1-thiol) were used to form self-assembled monolayers (SAMs) on silver, which influenced a fusion of multilamellar vesicles and the formation of tBLMs. Spectroscopic analysis by SERS and RAIRS has shown that by using different-length backfiller molecules, it is possible to control WC14 anchor molecules orientation on the surface. An introduction of increasingly longer surface backfillers in the mixed SAM may be related to the increasing SAMs molecular order and more vertical orientation of WC14 at both the hydrophilic ethylenoxide segment and the hydrophobic lipid bilayer anchoring alkane chains. Since no clustering of WC14 alkane chains, which is deleterious for tBLM integrity, was observed on dry samples, the suitability of mixed-component SAMs for subsequent tBLM formation was further interrogated by electrochemical impedance spectroscopy (EIS). EIS showed the arrangement of well-insulating tBLMs if 3M1P was used as a backfiller. An increase in the length of the backfiller led to increased defectiveness of tBLMs. Despite variable defectiveness, all tBLMs responded to the pore-forming cholesterol-dependent cytolysin, vaginolysin in a manner consistent with the functional reconstitution of the toxin into phospholipid bilayer. This experiment demonstrates the biological relevance of tBLMs assembled on silver surfaces and indicates their utility as biosensing elements for the detection of pore-forming toxins in liquid samples.
tethered bilayer lipid membranes (tBLMs) 作为蛋白质-膜相互作用研究的稳定且多功能的实验平台已为人所知。在这项工作中,研究了在银基底上组装功能性 tBLMs 以及回补分子的分子链长度对其性质的影响。使用以下回补分子 3-巯基-1-丙醇(3M1P)、4-巯基-1-丁醇(4M1B)、6-巯基-1-己醇(6M1H)和 9-巯基-1-壬醇(9M1N)与分子锚定物 WC14(20-十四烷氧基-3,6,9,12,15,18,22-七氧杂二十六烷-1-硫醇)混合,在银上形成自组装单层(SAMs),这影响了多层囊泡的融合和 tBLMs 的形成。通过 SERS 和 RAIRS 的光谱分析表明,通过使用不同长度的回补分子,可以控制 WC14 锚定物在表面上的取向。在混合 SAM 中引入越来越长的表面回补分子可能与 SAM 分子的有序性增加以及 WC14 在亲水乙氧基段和疏水脂质双层锚定烷烃链上的更垂直取向有关。由于在干燥样品中未观察到 WC14 烷烃链的聚集,这对 tBLM 完整性有害,因此通过电化学阻抗谱(EIS)进一步询问了混合成分 SAM 后续 tBLM 形成的适用性。EIS 表明,如果使用 3M1P 作为回补分子,则可以形成排列良好的绝缘 tBLM。回补分子长度的增加导致 tBLM 的缺陷性增加。尽管缺陷性不同,但所有 tBLM 对形成孔的胆固醇依赖性细胞溶素 vaginolysin 的反应方式均与毒素在磷脂双层中的功能重建一致。该实验证明了在银表面上组装的 tBLMs 的生物学相关性,并表明它们可用作生物传感器元件,用于检测液体样品中的形成孔毒素。