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Molecular mechanism underlying the selective attack of trehalose lipids on cancer cells as revealed by coarse-grained molecular dynamics simulations

机译:通过粗粒分子动力学模拟揭示的海藻糖脂质对海藻糖脂质的选择性发作的分子机制

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摘要

The present study indicated that the mixed lipid bilayer of dimyristoylphosphatidylcholine (DMPC) and trehalosemonomyristate (TreC14) interacted strongly with the plasma membrane of cancer cells, and not that of normal cells, when the composition of TreC14 was 70%, as revealed by coarse-grained molecular dynamics simulations. These results were consistent with those of previous experimental studies, indicating that DMPC/TreC14 mixed liposomes (DMTreC14) with TreC14 composition at 70% exhibited a strong anti-cancer effect without affecting normal cells. The simulations also revealed that lipids with highly hydrophilic and bulky head groups, such as TreC14, phosphatidylinositol (PI), and phosphatidylserine (PS), showed the tendency to accumulate. This caused both the DMTreC14 and cancer cell membranes to bend into large positive curvatures, resulting in tight contact between them. In contrast, no apparent interaction between the DMTreC14 and normal cell membranes was observed because PI and PS did not exist in the extracellular monolayer of the normal cell membrane.
机译:本研究表明,Divyrestoylpholline(DMPC)和海参的混合脂质双层(DMPC)和海参血细胞酯(TREC14)与癌细胞的质膜强烈相互作用,而不是正常细胞,当TREC14的组成为70%时,如粗 - 颗粒分子动力学模拟。这些结果与先前的实验研究的结果一致,表明DMPC / TREC14混合脂质体(DMTREC14)在70%的TREC14组合物中表现出强烈的抗癌作用而不影响正常细胞。该模拟还揭示了具有高亲水性和庞大的头部的脂质,例如TREC14,磷脂酰肌醇(PI)和磷脂酰丝氨酸(PS),显示出积聚的趋势。这导致DMTRec14和癌细胞膜弯曲成大的正曲率,导致它们之间的紧密接触。相反,观察到DMTREC14和正常细胞膜之间的明显相互作用,因为在正常细胞膜的细胞外单层中不存在PI和PS。

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