Biophysics of Ultrasound and Cell Interactions

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。这个基础科学计划将探索细胞膜的基本和复杂的生物成分在没有和存在微泡的情况下如何对超声波暴露做出反应，微泡可以一起损害和摧毁细胞。我们将使用低频(5-10 MHz)、中频(10-20 MHz)和高频(20-80 MHz)超声波进行研究。在这项研究计划中，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。我们将对人类细胞和基因表达谱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。将改变的声学参数将包括测量将包括超声频率、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可能参与相关信号转导和细胞膜修复的相关遗传途径和第二信息的诱导。我们的研究计划将采取一种有组织的方法，首先从细胞膜成分开始，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有助于超声介导的刺激的生物学反应。这一研究项目的新奇之处在于，它结合了超声波最初开发时尚未获得的现代生物技术，以及能够输送超声波的现代高灵敏度超声设备和微泡技术。它还解决了超声反应的一个方面，这还不是很好地理解。这项研究的意义在于，它将为理解生物标本对超声波的反应提供基本的基础。

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 program will probe how fundamental and complex biological components of cell membranes 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 program 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 human cells and gene expression profiling 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 messages that may be involved in relevant signal transduction and cell membrane repair. Our research program will take an organized approach beginning first with cell membrane components, then their more complex organizations and then their importance in cell signalling pathways. At the end of this research program we hope to be able to comprehend how cellular features, and molecular interactions contribute to biological responses to ultrasound-mediated stimulation. The novelty of this research program is that it combines modern biological techniques not available when ultrasound was initially developed and modern highly-sensitive ultrasound equipment and microbubble-technology capable of delivering ultrasound. It also addresses an aspect of ultrasound response which is not well understood. The significance of this research is that it will provide a fundamental basis for understanding responses to ultrasound from biological specimens.