Molecular Mechanism of the Cell Membrane Pore Formation Induced by Bubble Stable Cavitation.
Molecular Mechanism of the Cell Membrane Pore Formation Induced by Bubble Stable Cavitation.
复制标题
气泡稳定空化诱导细胞膜孔隙形成的分子机制。
DOI：
10.1021/acs.jpcb.8b09391
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Nguyen,PhuongH
中科院分区：
文献类型：
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作者：
Man,VietHoang;Truong,PhanMinh;Li,MaiSuan;Wang,Junmei;Van-Oanh,Nguyen-Thi;Derreumaux,Philippe;Nguyen,PhuongH
微泡结合超声提供了一种新的和有前途的方式将药物输送到活细胞中。据信，在超声下气泡的稳定振动或破裂是诱导细胞膜中形成孔的两个主要机制，药物可以通过孔进入细胞质内。气泡破裂假说不仅是直观的，因为释放的冲击波可以很容易地穿透并在膜中产生孔隙，而且它也被实验和理论所证实。相比之下，稳定振动的分子机制还没有得到很好的理解，因为实验困难，造成的脆弱性气泡和缺乏分子动力学模拟研究。为了更好地理解这一机制，我们开发了一个脂质涂层的气泡模型，我们应用于模拟稳定的空化的气泡中存在的脂质双层。我们表明，由气泡振动产生的壁面剪切应力不会引起膜孔的形成。相反，气泡与膜融合，随后的空化作用将脂质分子从膜中拉出，形成孔隙。这可以帮助人们选择泡壳材料、超声频率和强度的最佳组合，使得孔的打开和关闭将被优化。
Microbubbles in combination with ultrasound provide a new and promising way to deliver drugs into living cells. It is believed that the stable vibration or the collapse of the bubbles under ultrasound are the two main mechanisms that induce the formation of pores in the cell membranes, through which drugs may get inside the cell cytoplasm. The bubble collapse hypothesis is not only intuitive since released shock waves can easily penetrate and create pores in the membrane, but it is also confirmed by both experiment and theory. In contrast, the molecular mechanism of stable vibration is not well-understood because of experimental difficulties resulting from the fragility of bubbles and the lack of molecular dynamics simulation studies. To obtain a better understanding of this mechanism, we developed a lipid-coated bubble model that we applied to simulate the stable cavitation of the bubble in the presence of a lipid bilayer. We show that the wall shear stress generated by the bubble vibration does not induce the membrane pore formation. Instead, the bubble fuses with the membrane and subsequent cavitation pulls lipid molecules out of the membrane, creating pores. This could help one to choose the best combination of the bubble shell materials, the ultrasound frequency, and intensity, so that the opening and closing of pores will be optimized.