基于AFM的细胞表面超微形貌成像与机械特性测量研究进展

原子力显微镜(AFM)以其独特的优势(纳米级空间分辨率、皮牛级力灵敏度、免标记、可在溶液下工作)成为细胞生物学的重要研究手段.AFM不仅可以对活细胞表面超微形貌进行可视化表征,同时还可通过压痕技术对细胞机械特性(如杨氏模量)进行定量测量,为原位探索纳米尺度下单个活细胞动态生理活动及力学行为提供了可行性.过去的数十年中,研究人员利用AFM在细胞超微形貌成像和机械特性测量方面开展了广泛的应用研究,展示了有关细胞生理活动的大量新认识,为生命医药学领域相关问题的解决提供了新的思路;同时AFM自身的性能也在不断得到改进和提升,进一步促进了其在生命科学领域的应用.本文结合作者在应用AFM观测纳米尺度下癌症靶向药物作用效能方面的研究工作,介绍了AFM成像与细胞机械特性测量的原理,总结了近年来AFM用于细胞表面超微形貌成像与机械特性测量所取得的进展,讨论了AFM表征与检测细胞生理特性存在的问题,并对其未来发展方向进行了展望.

In situ Imaging The Cellular Ultra-microstructures and Measuring The Cellular Mechanical Properties Using Atomic Force Microscopy

Due to the unique advantages (e.g., nanometer spatial resolution, picoNewton force sensitivity, label-free, can work in aqueous conditions), atomic force microscopy(AFM) has become an important instrument in cell biology. AFM can not only visualize the ultra-microstructures on the surface of living cells, but also can quantify the cellular mechanical properties (such as Young's modulus) by indenting technique, opening the doors to in situ explore the dynamical physiological activities and mechanical behaviors of single living cells at the nanoscale. In the past decades, researchers have carried out extensive investigations in imaging the cellular ultra-microstructures and measuring the cellular mechanical properties using AFM, yielding novel insights into our understanding of cellular physiological activities and providing a new idea to solve the related issues in the field of biomedicine. The AFM's own performances have also been steadily improved, which further promote its applications in biology. In this paper, based on our own research in investigating the killing effects of targeted cancer drugs at the nanoscale using AFM, the principle of AFM imaging and measuring the cellular mechanical properties was presented, the progress in visualizing the cellular ultra-microstructures and quantifying the cellular mechanical properties using AFM was summarized, the challenges facing AFM single-cell assay and its future directions were discussed.