Department of Physics and Randall Centre for Cell and Molecular Biophysics, King's College London, WC2R 2LS, London, UK.
Chem Soc Rev. 2020 Oct 7;49(19):6816-6832. doi: 10.1039/d0cs00426j. Epub 2020 Sep 15.
Mechanical forces regulate a large variety of cellular functionalities, encompassing e.g. motility, differentiation and muscle contractility. To adapt to the dynamic change in mechanical stress, the constitutive individual proteins need to reversibly stretch and recoil over long periods of time. Yet, the molecular mechanisms controlling the mechanical unfolding and refolding of proteins cannot be accessed by protein folding biochemistry experiments conducted in the bulk, because they cannot typically apply forces to individual proteins. The advent of single-molecule nanomechanical techniques, often combined with bespoke protein engineering strategies, has enabled monitoring the conformational dynamics of proteins under force with unprecedented length-, time- and force-resolution. This review focuses on the fundamental operational principles of the main single-molecule nanomechanical techniques, placing particular emphasis on the most common analytical approaches used to extract information directly from the experiments. The breadth of enabling applications highlights the most exciting and promising outputs from the nanomechanics field to date.
机械力调节着大量的细胞功能，例如运动性、分化和肌肉收缩性。为了适应机械应力的动态变化，组成个体蛋白需要在很长一段时间内可逆地拉伸和回弹。然而，通过在整体中进行的蛋白质折叠生物化学实验，无法获得控制蛋白质机械展开和重折叠的分子机制，因为它们通常无法对单个蛋白质施加力。单分子纳米力学技术的出现，通常与定制的蛋白质工程策略相结合，使我们能够以前所未有的长度、时间和力分辨率监测力下蛋白质的构象动力学。这篇综述重点介绍了主要单分子纳米力学技术的基本操作原理，特别强调了从实验中直接提取信息的最常见分析方法。广泛的应用使人们看到了迄今为止纳米力学领域最令人兴奋和最有前途的成果。
