Ibsen Stuart, Mora Ruben, Shi Guixin, Schutt Carolyn, Cui Wenjin, Benchimol Michael, Serra Viviana, Esener Sadik
Department of Bioengineering, Moores Cancer Center, University of California San Diego, 3855 Health Sciences Dr. # 0815, La Jolla, CA, 92093-0815, USA.
Department of Biology, University of California San Diego, La Jolla, CA, 92093, USA.
J Biol Phys. 2017 Dec;43(4):493-510. doi: 10.1007/s10867-017-9465-4. Epub 2017 Nov 9.
Gas-filled microbubbles attached to cell surfaces can interact with focused ultrasound to create microstreaming of nearby fluid. We directly observed the ultrasound/microbubble interaction and documented that under certain conditions fluorescent particles that were attached to the surface of live cells could be removed. Fluorescently labeled liposomes that were larger than 500 nm in diameter were attached to the surface of endothelial cells using cRGD targeting to αvβ3 integrin. Microbubbles were attached to the surface of the cells through electrostatic interactions. Images taken before and after the ultrasound exposure were compared to document the effects on the liposomes. When exposed to ultrasound with peak negative pressure of 0.8 MPa, single microbubbles and groups of isolated microbubbles were observed to remove targeted liposomes from the cell surface. Liposomes were removed from a region on the cell surface that averaged 33.1 μm in diameter. The maximum distance between a single microbubble and a detached liposome was 34.5 μm. Single microbubbles were shown to be able to remove liposomes from over half the surface of a cell. The distance over which liposomes were removed was significantly dependent on the resting diameter of the microbubble. Clusters of adjoining microbubbles were not seen to remove liposomes. These observations demonstrate that the fluid shear forces generated by the ultrasound/microbubble interaction can remove liposomes from the surfaces of cells over distances that are greater than the diameter of the microbubble.
附着在细胞表面的充气微泡可与聚焦超声相互作用，使附近的流体产生微流。我们直接观察了超声/微泡相互作用，并记录了在某些条件下，附着在活细胞表面的荧光颗粒能够被去除。直径大于500nm的荧光标记脂质体通过靶向αvβ3整合素的cRGD附着在内皮细胞表面。微泡通过静电相互作用附着在细胞表面。比较超声暴露前后拍摄的图像，以记录对脂质体的影响。当暴露于峰值负压为0.8MPa的超声时，观察到单个微泡和孤立微泡组可从细胞表面去除靶向脂质体。脂质体从细胞表面平均直径为33.1μm的区域被去除。单个微泡与分离的脂质体之间的最大距离为34.5μm。单个微泡能够从细胞表面一半以上的区域去除脂质体。脂质体被去除的距离显著取决于微泡的静态直径。未观察到相邻微泡簇去除脂质体的情况。这些观察结果表明，超声/微泡相互作用产生的流体剪切力能够在大于微泡直径的距离上从细胞表面去除脂质体。
