Hippo Pathway and the role of Mechanical Tension in Cell Volume Regulation


Animal cells use an unknown mechanism to control their growth and physical size. Here, using the microfluidic 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 quantitatively explore the connection between cell mechanical tension and the mammalian Hippo pathway. We discover that the Hippo pathway influences cell volume by changing cell division volume in an mTOR independent manner. Moreover, changing cell tension by influencing myosin assembly can slow down cell cycle progression. These findings suggest that the mechanical behavior of the cell and the Hippo pathway are combined to control cell volume. There likely exists a tension-dependent cell cycle checkpoint that feeds back to cell growth control.

Rizal F. Hariadi
Johns Hopkins University
Sean Sun
Wednesday, February 20, 2019