Biophysical Fundamentals of Ultrasound Bioeffects

尽管在过去的五十年里，超声波已经被使用了，但对细胞和亚细胞成分对超声波的反应仍然知之甚少。这项基础科学计划将探索在没有和存在微泡的情况下，细胞的基本和复杂的生物成分如何对超声波暴露做出反应，这些微泡可能会一起损害和摧毁细胞。在这项研究中，我们将使用低频(5-10 MHz)、中频(10-20 MHz)和高频(20-80 MHz)超声波。*在本研究计划中，我们将探索细胞内的材料如何通过微泡对细胞膜的诱导作用来对超声波辐射做出反应。我们将对酵母和人类细胞使用细胞生物学技术，以更好地了解细胞内部的哪些特征负责细胞对超声波的反应。*声学参数将包括测量，包括超声频率、超声压力、超声脉冲持续时间和微泡浓度。我们将使用标准的生物形态测量方法，包括光学和电子显微镜，结合生物超微结构的图像分析，研究由多种人类细胞类型组成的生物标本及其对超声波和超声介导性微泡刺激的反应，以将生物特征与超声波暴露联系起来。我们还将使用基因表达方法来研究相关遗传途径和可能参与相关信号转导的第二信使的诱导。*我们的研究计划将采取有组织的方法，首先从总的生物成分开始，然后是它们更复杂的组织，然后是它们在细胞信号通路中的重要性。在这项研究计划结束时，我们希望能够理解细胞特征和分子相互作用如何对超声介导性刺激的生物反应做出贡献。

Although ultrasound has been used for the past fifty years it still remains poorly understood how cells and subcellular constituents react to ultrasound exposure. This fundamental basic science programme will probe how fundamental and complex biological components of cells react to ultrasound exposure in the absence and presence of microbubbles which can damage and destroy cells together. We will use low-frequency (5-10 MHz), mid-frequency (10-20 MHz) and high-frequency (20-80 MHz) ultrasound for this research.****In this research programme we will explore how materials inside cells react to ultrasound exposure through microbubble-induced effects on cell membranes. We will use cell biology techniques with yeast and human cells to better understand what features inside cells are responsible for cell responses to ultrasound. ****Acoustic parameters that will be varied will include measurements will include ultrasound frequency, ultrasound pressure, ultrasound pulse duration and microbubble concentration. We will study biological specimens consisting of a number of human cell types and their responses to ultrasound and ultrasound-mediated microbubble stimulation using standard measures of biological configuration including light and electron-microscopy combined with image analyses of biological ultrastructure to correlate biological features to ultrasound exposure. We will also use gene expression methodology to study the induction of related genetic pathways and second messengers that may be involved in relevant signal transduction.****Our research programme will take an organized approach beginning first with gross biological constituents, then their more complex organizations and then their importance in cell signalling pathways. At the end of this research programme we hope to be able to comprehend how cellular features, and molecular interactions contribute to biological responses to ultrasound-mediated stimulation.********