Department of Chemical Sciences, Tata Institute of Fundamental Research, Dr. Homi Bhabha Road, Colaba, Mumbai 400005, India.
Emerg Top Life Sci. 2021 May 14;5(1):103-111. doi: 10.1042/ETLS20200255.
Single-molecule force spectroscopy (SMFS) is an emerging tool to investigate mechanical properties of biomolecules and their responses to mechanical forces, and one of the most-used techniques for mechanical manipulation is the atomic force microscope (AFM). AFM was invented as an imaging tool which can be used to image biomolecules in sub-molecular resolution in physiological conditions. It can also be used as a molecular force probe for applying mechanical forces on biomolecules. In this brief review, we will provide exciting examples from recent literature which show how the advances in AFM have enabled us to gain deep insights into mechanical properties and mechanobiology of biomolecules. AFM has been applied to study mechanical properties of cells, tissues, microorganisms, viruses as well as biological macromolecules such as proteins. It has found applications in biomedical fields like cancer biology, where it has been used both in the diagnostic phases as well as drug discovery. AFM has been able to answer questions pertaining to mechanosensing by neurons, and mechanical changes in viruses during infection by the viral particles as well as the fundamental processes such as cell division. Fundamental questions related to protein folding have also been answered by SMFS like determination of energy landscape properties of variety of proteins and their correlation with their biological functions. A multipronged approach is needed to diversify the research, as a combination with optical spectroscopy and computer-based steered molecular dynamic simulations along with SMFS can help us gain further insights into the field of biophysics and modern biology.
单分子力谱（SMFS）是一种新兴的工具，用于研究生物分子的机械性质及其对机械力的响应，而最常用于机械操作的技术之一是原子力显微镜（AFM）。AFM 最初被发明为一种成像工具，可用于在生理条件下以亚分子分辨率成像生物分子。它也可以用作分子力探针，对生物分子施加机械力。在这篇简短的综述中，我们将提供来自最近文献的令人兴奋的例子，展示 AFM 的进展如何使我们能够深入了解生物分子的机械性质和机械生物学。AFM 已被应用于研究细胞、组织、微生物、病毒以及生物大分子（如蛋白质）的机械性能。它在癌症生物学等生物医学领域有应用，在诊断阶段和药物发现中都有应用。AFM 能够回答有关神经元机械感应的问题，以及病毒在感染过程中机械变化以及细胞分裂等基本过程。SMFS 还回答了与蛋白质折叠相关的基本问题，例如确定各种蛋白质的能量景观特性及其与生物功能的相关性。需要采用多管齐下的方法来使研究多样化，因为与光学光谱学和基于计算机的导向分子动力学模拟相结合的 AFM 可以帮助我们更深入地了解生物物理学和现代生物学领域。
