Homeostatic pressure of a proliferating multicellular foam with hydromechanical volume regulation.

The dynamics of tumor growth and its competition with host tissue depend not only on proliferation rates but also on the mechanical properties of individual cells. Here, we present a hydromechanical model that couples osmotic volume regulation to tissue mechanics, representing multicellular aggregates as a proliferating foam of interacting cells. In confined conditions, we simulate multicellular growth until reaching a hydromechanical steady-state with a compressive multicellular stress. Next, we show that both increased adhesive tension and reduced surface tension increase the homeostatic pressure of a growing aggregate. This mechanical advantage allows softer and more adhesive cells to outcompete stiffer and even faster-growing populations. Our results demonstrate that single-cell mechanics can override proliferation rate in determining growth dynamics and competitive outcomes in multicellular aggregates.