School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, United States.
Cell Imaging Center, Office of Research and Innovation, Drexel University, PA 19104, United States.
Prog Biophys Mol Biol. 2022 Dec;176:67-81. doi: 10.1016/j.pbiomolbio.2022.08.005. Epub 2022 Aug 30.
Mechanosensing at the interface of a cell and its surrounding microenvironment is an essential driving force of physiological processes. Understanding molecular activities at the cell-matrix interface has the potential to provide novel targets for improving tissue regeneration and early disease intervention. In the past few decades, the advancement of atomic force microscopy (AFM) has offered a unique platform for probing mechanobiology at this crucial microdomain. In this review, we describe key advances under this topic through the use of an integrated system of AFM (as a biomechanical testing tool) with complementary immunofluorescence (IF) imaging (as an in situ navigation system). We first describe the body of work investigating the micromechanics of the pericellular matrix (PCM), the immediate cell micro-niche, in healthy, diseased, and genetically modified tissues, with a focus on articular cartilage. We then summarize the key findings in understanding cellular biomechanics and mechanotransduction, in which, molecular mechanisms governing transmembrane ion channel-mediated mechanosensing, cytoskeleton remodeling, and nucleus remodeling have been studied in various cell and tissue types. Lastly, we provide an overview of major technical advances that have enabled more in-depth studies of mechanobiology, including the integration of AFM with a side-view microscope, multiple optomicroscopy, a fluorescence recovery after photobleaching (FRAP) module, and a tensile stretching device. The innovations described here have contributed greatly to advancing the fundamental knowledge of extracellular matrix biomechanics and cell mechanobiology for improved understanding, detection, and intervention of various diseases.
细胞与其周围微环境的界面处的机械感知是生理过程的基本驱动力。了解细胞-基质界面处的分子活动有可能为改善组织再生和早期疾病干预提供新的靶点。在过去的几十年中，原子力显微镜（AFM）的进步为在这个关键的微域中探测机械生物学提供了一个独特的平台。在这篇综述中，我们通过使用 AFM （作为生物力学测试工具）与互补的免疫荧光（IF）成像（作为原位导航系统）的集成系统，描述了该主题下的关键进展。我们首先描述了研究细胞外基质（PCM）的微力学的工作，PCM 是细胞的微微环境，重点是关节软骨，包括健康、患病和基因修饰组织中的工作。然后，我们总结了理解细胞生物力学和力学转导的关键发现，其中研究了跨膜离子通道介导的机械感知、细胞骨架重塑和核重塑的分子机制，研究了各种细胞和组织类型。最后，我们概述了使机械生物学的更深入研究成为可能的主要技术进步，包括将 AFM 与侧视显微镜、多光显微镜、荧光恢复后光漂白（FRAP）模块和拉伸拉伸装置集成。这里描述的创新极大地促进了细胞外基质生物力学和细胞力学生物学的基本知识的发展，有助于提高对各种疾病的理解、检测和干预。
