Potential blockade of the human voltage-dependent anion channel by MoS2 nanoflakes.
Potential blockade of the human voltage-dependent anion channel by MoS2 nanoflakes.
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DOI：
10.1039/c9cp00195f
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发表时间：
2019-05
期刊：
影响因子：
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通讯作者：
Zonglin Gu;Wei Song;Shengtang Liu;Baoyu Li;L. Plant;Xuanyu Meng
中科院分区：
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作者：
Zonglin Gu;Wei Song;Shengtang Liu;Baoyu Li;L. Plant;Xuanyu Meng
尽管人们对二硫化钼 (MoS2) 纳米材料特别是在生物医学领域产生了浓厚的兴趣，但其生物效应尚未得到充分研究。在这里，我们采用计算和功能相结合的方法，探讨了 MoS2 纳米片对普遍存在的线粒体孔蛋白电压依赖性阴离子通道 (VDAC1) 的影响。全原子分子动力学模拟表明，MoS2 纳米片与人类 VDAC1 发生特定的接触相互作用。我们表明，hVDAC1 和纳米片之间的初始接触是疏水性的，但随后通过平衡状态下范德华 (vdW)、疏水性和静电相互作用的复杂相互作用而增强。此外，MoS2纳米片可以插入hVDAC1孔的内腔中。通过平均力 (PMF) 势计算的自由能计算验证了 MoS2-hVDAC1 复合物的封闭构型比非封闭结合模式在能量上更有利。与这些预测一致，我们发现 MoS2 使线粒体膜电位 (Ψm) 去极化，并导致哺乳动物组织培养细胞的活力下降。这些发现可能为 MoS2 纳米材料的潜在生物效应提供新的线索。
Despite significant interest in molybdenum disulfide (MoS2) nanomaterials, particularly in biomedicine, their biological effects have been understudied. Here, we explored the effect of MoS2 nanoflakes on the ubiquitous mitochondrial porin voltage-dependent anion channel (VDAC1), using a combined computational and functional approach. All-atomic molecular dynamics simulations suggest that MoS2 nanoflakes make specific contact interactions with human VDAC1. We show that the initial contacts between hVDAC1 and the nanoflake are hydrophobic but are subsequently enhanced by a complex interplay of van der Waals (vdW), hydrophobic and electrostatic interactions in the equilibrium state. Moreover, the MoS2 nanoflake can insert into the lumen of the hVDAC1 pore. Free-energy calculations computed by the potential of mean force (PMF) verify that the blocked configuration of the MoS2-hVDAC1 complex is more energetically favorable than the non-blocked binding mode. Consistent with these predictions, we showed that MoS2 depolarizes the mitochondrial membrane potential (Ψm) and causes a decrease in the viability of mammalian tissue culture cells. These findings might shed new light on the potential biological effect of MoS2 nanomaterials.