Controlling Cellular Volume via Mechanical and Physical Properties of Substrate

The mechanical and physical properties of substrate play a crucial role in regulating many cell functions and behaviors. However, how these properties affect cell volume is still unclear. Here, we show that an increase in substrate stiffness, available spread area, or effective adhesion energy density results in a remarkable cell volume decrease (up to 50%), and the dynamic cell spreading process is also accompanied by dramatic cell volume decrease. Further, studies of ion channel inhibition and osmotic shock suggest that these volume decreases are due to the efflux of water and ions. We also show that disrupting cortex contractility leads to bigger cell volume. Collectively, these results reveal the "mechanism of adhesion-induced compression of cells," i.e., stronger interaction between cell and substrate leads to higher actomyosin contractility, expels water and ions, and thus decreases cell volume.