TY - JOUR
T1 - Molecular Mechanism of the Cell Membrane Pore Formation Induced by Bubble Stable Cavitation
AU - Man, Viet Hoang
AU - Truong, Phan Minh
AU - Li, Mai Suan
AU - Wang, Junmei
AU - Van-Oanh, Nguyen Thi
AU - Derreumaux, Philippe
AU - Nguyen, Phuong H.
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jpcb.8b09391
DO - 10.1021/acs.jpcb.8b09391
M3 - Article
C2 - 30540473
AN - SCOPUS:85059621792
SN - 1520-6106
VL - 123
SP - 71
EP - 78
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 1
ER -