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首页> 外文期刊>IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control >Characterization of cell membrane response to ultrasound activated microbubbles
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Characterization of cell membrane response to ultrasound activated microbubbles

机译：表征细胞膜对超声激活的微泡的反应

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Contrast agents for ultrasound imaging, composed of tiny gas microbubbles, have become a reality in clinical routine. They are extensively used in radiology for detection and characterization of various tumors and in cardiology for left ventricular opacification. Recent experimental studies showed that ultrasound waves in combination with contrast agent microbubbles increase transiently cell membrane permeability in a process known as sonoporation. This effect is thought to allow foreign molecules to enter the cell. In that context, we explored the cell membrane''s responses to microbubbles'' oscillations as the mechanism is not completely understood. Breast cancer cell line in combination with contrast microbubbles were used. Ultrasound was applied using a transducer of 1 MHz center frequency transmitting a 10-cycle burst of different acoustic pressures repeated every 100 mus. Patch-clamp technique in whole cell configuration was used to explore transmembrane ion exchange through the variations in membrane potential. To characterize the activated ion channels, the variations of the intracellular calcium (Ca2+) concentration were explored using a fluorescent marker. The results revealed that ultrasound stimulation induces a rapid hyperpolarization of cell membrane potential when the microbubble is in direct contact with the cell, but the potential returned to its initial value when ultrasound stimulation stopped. The change in cell membrane potential indicates the activation of specific ion channels and depends on the quality of microbubble adhesion to the cell membrane. Microbubbles were shown to induce a mechanical stretch activating BKca channels. Simultaneous Ca2+ measurements indicate a slow and progressive Ca2+ increase that is likely a consequence of BKca channels opening not a cause. These results demonstrate that microbubbles'' oscillations under ultrasound activation entail modulation of cellular function and signaling by t-riggering the modulation of ionic transports through the cell membrane. Cells response to the mechanical stretch caused by gentle microbubble oscillations is characterized by the opening of BKca stretch channels and a Ca2+ flux, which might potentially trigger other cellular responses responsible for membrane sonopermeabilization.
机译：由微小的气体微气泡组成的超声成像造影剂已成为临床常规操作。它们广泛用于放射学中以检测和表征各种肿瘤，并在心脏病学中用于左心室混浊。最近的实验研究表明，超声波与造影剂微泡相结合会在称为声穿孔的过程中暂时增加细胞膜的通透性。认为该作用使外来分子进入细胞。在这种情况下，我们对细胞膜对微泡振荡的反应进行了探索，因为其机理尚不完全清楚。使用了乳腺癌细胞系和对比微泡。使用中心频率为1 MHz的换能器施加超声波，每100 mus重复发射10个周期的不同声压脉冲。全细胞结构中的膜片钳技术用于通过膜电位的变化探索跨膜离子交换。为了表征活化的离子通道，使用荧光标记物探索了细胞内钙（Ca2 +）浓度的变化。结果表明，当微泡直接与细胞接触时，超声刺激会引起细胞膜电位快速超极化，但是当超声刺激停止时，电势会返回其初始值。细胞膜电位的变化表明特定离子通道的激活，并取决于微泡粘附到细胞膜上的质量。已显示微泡诱导机械拉伸激活BKca通道。同时进行Ca2 +测量表明，Ca2 +缓慢而逐渐增加，这很可能是BKca通道开放的结果而不是原因。这些结果表明，超声激活下的微泡振荡需要调节细胞功能并通过t-rigging调节穿过细胞膜的离子传递来发出信号。细胞对由轻度微气泡振荡引起的机械拉伸的反应的特征是BKca拉伸通道的开放和Ca2 +通量的形成，这可能潜在地触发其他负责膜超声操作的细胞反应。

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