Friedrich Oliver, Merten Anna-Lena, Schneidereit Dominik, Guo Yang, Schürmann Sebastian, Martinac Boris
Institute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Mechanosensory Biophysics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
Front Bioeng Biotechnol. 2019 Mar 27;7:55. doi: 10.3389/fbioe.2019.00055. eCollection 2019.
Mechanobiology is a rapidly growing interdisciplinary research field, involving biophysics, molecular and cell biology, biomedical engineering, and medicine. Rapid progress has been possible due to emerging devices and tools engineered for studies of the effect of mechanical forces, such as stretch or shear force, impacting on biological cells and tissues. In response to such mechanical stimuli, cells possess various mechanosensors among which mechanosensitive ion channels are molecular transducers designed to convert mechanical stimuli into electrical and/or biochemical intracellular signals on millisecond time scales. To study their role in cellular signaling pathways, devices have been engineered that enable application of different strain protocols to cells allowing for determination of the stress-strain relationship or other, preferably optical, readouts. Frequently, these devices are mounted on fluorescence microscopes, allowing simultaneous investigation of cellular mechanotransduction processes combined with live-cell imaging. Mechanical stress in organs/tissues can be complex and multiaxial, e.g., in hollow organs, like lung alveoli, bladder, or the heart. Therefore, biomedical engineers have, in recent years, developed devices based on elastomeric membranes for application of biaxial or multiaxial stretch to 2D substrate-adhered or even 3D-embedded cells. Here, we review application of stretch technologies to cellular mechanotransduction with a focus on cardiovascular systems. We also present new results obtained by our device to examine mechanosensitivity of adult ventricular cardiomyocytes. We show that sudden isotropic stretch of cardiomyocytes can already trigger arrhythmic Ca transients on the single cell level.
机械生物学是一个快速发展的跨学科研究领域,涉及生物物理学、分子与细胞生物学、生物医学工程和医学。由于出现了用于研究诸如拉伸或剪切力等机械力对生物细胞和组织影响的设备和工具,快速进展才成为可能。响应此类机械刺激,细胞拥有各种机械传感器,其中机械敏感离子通道是分子换能器,旨在在毫秒时间尺度上将机械刺激转化为电和/或生化细胞内信号。为了研究它们在细胞信号通路中的作用,已设计出能够对细胞施加不同应变方案的设备,从而能够确定应力 - 应变关系或其他(最好是光学的)读数。通常,这些设备安装在荧光显微镜上,允许同时研究细胞机械转导过程并结合活细胞成像。器官/组织中的机械应力可能是复杂且多轴的,例如在中空器官中,如肺泡、膀胱或心脏。因此,近年来生物医学工程师开发了基于弹性体膜的设备,用于对二维基质粘附甚至三维嵌入的细胞施加双轴或多轴拉伸。在这里,我们回顾拉伸技术在细胞机械转导中的应用,重点是心血管系统。我们还展示了通过我们的设备获得的新结果,以检查成年心室心肌细胞的机械敏感性。我们表明,心肌细胞的突然各向同性拉伸已经可以在单细胞水平上触发心律失常性钙瞬变。