The widespread use of organophosphate flame retardants (OPFRs), a serious type of pervasive environmental contaminants, has led to a global concern regarding their diverse toxicities to living beings. Using a combination of experimental and theoretical approaches, we systematically studied the adsorption, accumulation, and influence of a series of OPFRs on the lipid membranes of bacteria and cells. Our results revealed that OPFRs can aggregate in lipid membranes, leading to the destruction of membrane integrity. During this process, the molecular structure of the OPFRs is a dominant factor that significantly influences the strength of their interaction with the lipid membrane, resulting in varying degrees of biotoxicity. Triphenyl phosphate (TPHP), owing to its large molecular size and strong hydrophobicity, causes severe membrane disruption through the formation of nanoclusters. The corresponding severe toxicity originates from the phase transitions of the lipid membranes. In contrast, smaller OPFRs such as triethyl phosphate (TEP) and tris(2-chloroethyl) phosphate (TCEP) have weaker hydrophobicity and induce minimal membrane disturbance and ineffective damage. In vivo, gavage of TPHP induced more severe barrier damage and inflammatory infiltration in mice than TEP or TCEP, confirming the higher toxicity of TPHP. Overall, our study elucidates the structure-dependent adsorption of OPFRs onto lipid membranes, highlighting their destructive interactions with membranes as the origin of OPFR toxicity.

中文翻译：

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有机磷酸酯阻燃剂在脂质膜上的结构依赖性破坏性吸附


有机磷酸酯阻燃剂（OPFR）是一种严重的普遍环境污染物，其广泛使用已引起全球对其对生物的多种毒性的关注。我们采用实验和理论相结合的方法，系统地研究了一系列OPFRs对细菌和细胞脂质膜的吸附、积累和影响。我们的结果表明，OPFR 可以在脂质膜中聚集，导致膜完整性遭到破坏。在此过程中，OPFRs的分子结构是一个主导因素，显着影响其与脂膜相互作用的强度，从而导致不同程度的生物毒性。磷酸三苯酯（TPHP）由于其大分子尺寸和强疏水性，通过形成纳米簇而导致严重的膜破坏。相应的严重毒性源于脂质膜的相变。相比之下，磷酸三乙酯（TEP）和磷酸三（2-氯乙基）酯（TCEP）等较小的OPFR具有较弱的疏水性，并且引起最小的膜干扰和无效损伤。在体内，与 TEP 或 TCEP 相比，灌胃 TPHP 在小鼠体内引起更严重的屏障损伤和炎症浸润，证实了 TPHP 具有更高的毒性。总的来说，我们的研究阐明了 OPFR 在脂质膜上的结构依赖性吸附，强调它们与膜的破坏性相互作用是 OPFR 毒性的根源。