邻苯二甲酸酯(PAEs)是典型的环境内分泌干扰物,以非常低的浓度干扰生物体的内分泌系统。质膜是有机污染物进入生物体的第一道屏障,因此膜通透性是影响其生物毒性的关键因素。在这项研究中,基于计算方法,我们研究了典型PAEs(邻苯二甲酸二甲酯,DMP;邻苯二甲酸二丁酯,DBP;邻苯二甲酸二-2-乙基己酯,DEHP),以及它们对膜性能的影响,并揭示了相关的分子机制。我们的结果表明,PAEs可以自发进入膜,优选双层的头基-酰基链界面,侧链越长(DEHP>DBP>DMP),插入越深。与最短的DMP相比,DEHP明显增加膜厚度,订单,和刚性,这可能是由于其更强的疏水性。平均力(PMF)分析的潜力揭示了位于水膜界面的能量屏障的存在,在DEHP系统中获得的最大值为2.14kcalmol−1。因此,膜插入的难度也与PAE分子的侧链长度或疏水性呈正相关。这些发现将启发我们理解PAEs之间的结构-活性关系及其对膜性质的影响。为制定环境污染标准和防治小分子污染物提供科学依据。
Phthalic acid esters (PAEs) are typical environmental endocrine disrupters, interfering with the endocrine system of organisms at very low concentrations. The plasma membrane is the first barrier for organic pollutants to enter the organism, so membrane permeability is a key factor affecting their biological toxicity. In this study, based on computational approaches, we investigated the permeation and intramembrane aggregation of typical PAEs (dimethyl phthalate, DMP; dibutyl phthalate, DBP; di-2-ethyl hexyl phthalate, DEHP), as well as their effects on membrane properties, and related molecular mechanisms were uncovered. Our results suggested that PAEs could enter the membrane spontaneously, preferring the headgroup-acyl chain interface of the bilayer, and the longer the side chain (DEHP > DBP > DMP), the deeper the insertion. Compared with the shortest DMP, DEHP apparently increased membrane thickness, order, and rigidity, which might be due to its stronger hydrophobicity. Potential of means force (PMF) analysis revealed the presence of an energy barrier located at the water-membrane interface, with a maximum value of 2.14 kcal mol−1 obtained in the DEHP-system. Therefore, the difficulty of membrane insertion is also positively correlated with the side-chain length or hydrophobicity of PAE molecules. These findings will inspire our understanding of structure-activity relationship between PAEs and their effects on membrane properties, and provide a scientific basis for the formulation of environmental pollution standards and the prevention and control of small molecule pollutants.