School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), 50 UNIST-gil, Ulsan, 44919, Republic of Korea.
Division of Environmental Science and Engineering, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang, 37673, Republic of Korea.
J Hazard Mater. 2018 Jul 5;353:271-279. doi: 10.1016/j.jhazmat.2018.04.017. Epub 2018 Apr 12.
Various xenobiotics interact with biological membranes, and precise evaluations of the molecular interactions between them are essential to foresee the toxicity and bioavailability of existing or newly synthesized molecules. In this study, surface forces apparatus (SFA) measurement and Langmuir trough based tensiometry are performed to reveal nanomechanical interaction mechanisms between potential toxicants and biological membranes for ex vivo toxicity evaluation. As a toxicant, polyhexamethylene guanidine (PHMG) was selected because PHMG containing humidifier disinfectant and Vodka caused lots of victims in both S. Korea and Russia, respectively, due to the lack of holistic toxicity evaluation of PHMG. Here, we measured strong attraction (Wad ∼4.2 mJ/m) between PHMG and head group of biological membranes while no detectable adhesion force between the head group and control molecules was measured. Moreover, significant changes in π-A isotherm of 1,2-Dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) monolayers were measured upon PHMG adsorption. These results indicate PHMG strongly binds to hydrophilic group of lipid membranes and alters the structural and phase behavior of them. More importantly, complementary utilization of SFA and Langmuir trough techniques are found to be useful to predict the potential toxicity of a chemical by evaluating the molecular interaction with biological membranes, the primary protective barrier for living organisms.
各种外源性物质与生物膜相互作用,精确评估它们之间的分子相互作用对于预测现有或新合成分子的毒性和生物利用度至关重要。在这项研究中,使用表面力仪(SFA)测量和基于 Langmuir 槽的张力计来揭示潜在毒性物质与生物膜之间的纳米机械相互作用机制,以进行体外毒性评估。作为一种毒性物质,选择聚六亚甲基胍(PHMG),因为由于缺乏对 PHMG 的全面毒性评估,含有加湿器消毒剂的 PHMG 和 Vodka 分别在韩国和俄罗斯导致了大量受害者。在这里,我们测量了 PHMG 与生物膜头部基团之间的强吸引力(Wad∼4.2 mJ/m),而在头部基团和对照分子之间没有检测到可检测的粘附力。此外,在 PHMG 吸附后,1,2-二棕榈酰基-sn-甘油-3-磷酸胆碱(DPPC)单层的π-A 等温线发生了显著变化。这些结果表明 PHMG 与脂质膜的亲水头基强烈结合,并改变了它们的结构和相行为。更重要的是,发现 SFA 和 Langmuir 槽技术的互补利用可通过评估与生物膜的分子相互作用来预测化学物质的潜在毒性,生物膜是生物的主要保护屏障。