Cell mechanics are a biophysical indicator of cell state, such as cancer metastasis, leukocyte activation, and cell cycle progression. Atomic force microscopy (AFM) is a widely used technique to measure cell mechanics, where the Young modulus of a cell is usually derived from the Hertz contact model. However, the Hertz model assumes that the cell is an elastic, isotropic, and homogeneous material and that the indentation is small compared to the cell size. These assumptions neglect the effects of the cytoskeleton, cell size and shape, and cell environment on cell deformation. In this study, we investigated the influence of cell size on the estimated Young's modulus using liposomes as cell models. Liposomes were prepared with different sizes and filled with phosphate buffered saline (PBS) or hyaluronic acid (HA) to mimic the cytoplasm. AFM was used to obtain the force indentation curves and fit them to the Hertz model. We found that the larger the liposome, the lower the estimated Young's modulus for both PBS-filled and HA-filled liposomes. This suggests that the Young modulus obtained from the Hertz model is not only a property of the cell material but also depends on the cell dimensions. Therefore, when comparing or interpreting cell mechanics using the Hertz model, it is essential to account for cell size.

Department of Mechanics Biomechanics and Mechatronics Faculty of Mechanical Engineering Czech Technical University Prague Technická 4 16000 Prague Czech Republic

Department of Natural Sciences Faculty of Biomedical Engineering Czech Technical University Prague Náměstí Sítná 3105 27201 Kladno Czech Republic

Laboratory of Biophysics Faculty of Electrical Engineering University of Ljubljana Trzaska 25 1000 Ljubljana Slovenia

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