Harnessing atomic force microscopy-based single-cell analysis to advance physical oncology

Single-cell analysis is an emerging and promising frontier in the field of life sciences, which is expected to facilitate the exploration of fundamental laws of physiological and pathological processes. Single-cell analysis allows experimental access to cell-to-cell heterogeneity to reveal the distinctive behaviors of individual cells, offering novel opportunities to dissect the complexity of severe human diseases such as cancers. Among the single-cell analysis tools, atomic force microscopy (AFM) is a powerful and versatile one which is able to nondestructively image the fine topographies and quantitatively measure multiple mechanical properties of single living cancer cells in their native states under aqueous conditions with unprecedented spatiotemporal resolution. Over the past few decades, AFM has been widely utilized to detect the structural and mechanical behaviors of individual cancer cells during the process of tumor formation, invasion, and metastasis, yielding numerous unique insights into tumor pathogenesis from the biomechanical perspective and contributing much to the field of cancer mechanobiology. Here, the achievements of AFM-based analysis of single cancer cells to advance physical oncology are comprehensively summarized, and challenges and future perspectives are also discussed. RESEARCH HIGHLIGHTS: Achievements of AFM in characterizing the structural and mechanical behaviors of single cancer cells are summarized, and future directions are discussed. AFM is not only capable of visualizing cellular fine structures, but can also measure multiple cellular mechanical properties as well as cell-generated mechanical forces. There is still plenty of room for harnessing AFM-based single-cell analysis to advance physical oncology.