Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Int J Mol Sci. 2018 Mar 23;19(4):960. doi: 10.3390/ijms19040960.
One of the most successful applications of atomic force microscopy (AFM) in biology involves monitoring the effect of force on single biological molecules, often referred to as force spectroscopy. Such studies generally entail the application of pulling forces of different magnitudes and velocities upon individual molecules to resolve individualistic unfolding/separation pathways and the quantification of the force-dependent rate constants. However, a less recognized variation of this method, the application of compressive force, actually pre-dates many of these "tensile" force spectroscopic studies. Further, beyond being limited to the study of single molecules, these compressive force spectroscopic investigations have spanned samples as large as living cells to smaller, multi-molecular complexes such as viruses down to single protein molecules. Correspondingly, these studies have enabled the detailed characterization of individual cell states, subtle differences between seemingly identical viral structures, as well as the quantification of rate constants of functionally important, structural transitions in single proteins. Here, we briefly review some of the recent achievements that have been obtained with compressive force spectroscopy using AFM and highlight exciting areas of its future development.
原子力显微镜（AFM）在生物学中最成功的应用之一涉及监测力对单个生物分子的影响，通常称为力谱学。此类研究通常需要对单个分子施加不同大小和速度的拉力，以解析个体解折叠/分离途径，并量化力依赖性速率常数。然而，这种方法的一个较少被认识到的变体，即压缩力的应用，实际上早于许多这些“拉伸”力谱学研究。此外，这些压缩力谱学研究不仅限于单个分子的研究，还涵盖了从活细胞到更大的多分子复合物（如病毒），甚至单个蛋白质分子的研究。相应地，这些研究使我们能够详细表征单个细胞状态、看似相同的病毒结构之间的细微差异，以及量化单个蛋白质中功能重要的结构转变的速率常数。在这里，我们简要回顾了使用 AFM 进行压缩力谱学研究的一些最新成果，并强调了其未来发展的令人兴奋的领域。
