Animal cells use an unknown mechanism to control their growth and physical size. Here, using the fluorescence exclusion method, we measure cell volume for adherent cells on substrates of varying stiffness. We discover that the cell volume has a complex dependence on substrate stiffness and is positively correlated with the size of the cell adhesion to the substrate. From a mechanical force–balance condition that determines the geometry of the cell surface, we find that the observed cell volume variation can be predicted quantitatively from the distribution of active myosin through the cell cortex. To connect cell mechanical tension with cell size homeostasis, we quantified the nuclear localization of YAP/TAZ, a transcription factor involved in cell growth and proliferation. We find that the level of nuclear YAP/TAZ is positively correlated with the average cell volume. Moreover, the level of nuclear YAP/TAZ is also connected to cell tension, as measured by the amount of phosphorylated myosin. Cells with greater apical tension tend to have higher levels of nuclear YAP/TAZ and a larger cell volume. These results point to a size-sensing mechanism based on mechanical tension: the cell tension increases as the cell grows, and increasing tension feeds back biochemically to growth and proliferation control.
Dynamic-ultrastructural cell volume (3D) correlative microscopy facilitated by intracellular fluorescent nanodiamonds as multi-modal probes
