Atomic force microscopy for investigating cell and tissue mechanics as heterogeneous and hierarchical materials

Atomic force microscopy (AFM) has been extensively used to measure the mechanical properties of single cells and tissues with a high force sensitivity. AFM has been established to quantify mechanical differences between cells, e.g., between normal and disease cells, and between untreated (controlled) and treated cells. However, since these biological samples are intrinsically heterogeneous and hierarchical materials, AFM often suffers from the quantification of cell and tissue mechanics due to the high spatial resolution of AFM from the nanoscale to the microscale, comparable to the spatial variation and fluctuation of living systems. Thus, it is still challenging to elucidate universal nano- and micro-mechanical features of living systems using AFM data. This review addresses how AFM can quantify the heterogeneities and hierarchies of cell systems. For single-cell mechanical analysis, AFM has been combined with micropatterned substrate to control cell shape and precisely define the AFM measurement within cells, allowing us to analyze the cell-to-cell mechanical variation. For tissue mechanical analysis, we introduce AFM with a wide-scan range to map multicellular samples from a few hundred to millimeter scales, depending on the type of scanner, allowing us to quantify the spatial mechanical variation in multicellular systems. The reliability and the possibility of AFM to apply mechanics studies on cells and tissues with a range of Pascal (Pa) to MPa are addressed. © 2023 The Japan Society of Mechanical Engineers. This is an open access article under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/).