Durotaxis Index of 3T3 Fibroblast Cells Scales with Stiff-to-Soft Membrane Tension Polarity.

Cell durotaxis is an essential process in tissue development. Although the role of cytoskeleton in cell durotaxis has been widely studied, whether cell volume and membrane tension are implicated in cell durotaxis remains unclear. By quantifying the volume distribution during cell durotaxis, we show that the volume of 3T3 fibroblast cells decreases by almost 40% as cells migrate toward stiffer regions of gradient gels. Inhibiting ion transporters that can reduce the amplitude of cell volume decrease significantly suppresses cell durotaxis. However, from the correlation analysis, we find that durotaxis index does not correlate with the cell volume decrease. It scales with the membrane tension difference in the direction of stiffness gradient. Because of the tight coupling between cell volume and membrane tension, inhibition of Na+/K+ ATPase and Na+/H+ exchanger results in smaller volume decrease and membrane tension difference. Collectively, our findings indicate that the polarization of membrane tension is a central regulator of cell durotaxis, and Na+/K+ ATPase and Na+/H+ exchanger can help to maintain the membrane tension polarity.