Tissue evolution: Mechanical interplay of adhesion, pressure, and heterogeneity

The evolution of various competing cell types in tissues, and the resulting persistent tissue population, is studied numerically and analytically in a particle-based model of active tissues. Mutations change the properties of cells in various ways, including their mechanical properties. Each mutation results in an advantage or disadvantage to grow in the competition between different cell types. While changes in signaling processes and biochemistry play an important role, we focus on changes in the mechanical properties by studying the result of variation of growth force and adhesive cross-interactions between cell types. For independent mutations of growth force and adhesion strength, the tissue evolves towards cell types with high growth force and low internal adhesion strength, as both increase the homeostatic pressure. Motivated by biological evidence, we postulate a coupling between both parameters, such that an increased growth force comes at the cost of a higher internal adhesion strength or vice versa. This tradeoff controls the evolution of the tissue, ranging from unidirectional evolution to very heterogeneous and dynamic populations. The special case of two competing cell types reveals three distinct parameter regimes: Two in which one cell type outcompetes the other, and one in which both cell types coexist in a highly mixed state. Interestingly, a single mutated cell alone suffices to reach the mixed state, while a finite mutation rate affects the results only weakly. Finally, the coupling between changes in growth force and adhesion strength reveals a mechanical explanation for the evolution towards intra-tumor heterogeneity, in which multiple species coexist even under a constant evolutianary pressure

Mechanics of tissue competition: Interfaces stabilize coexistence

Mechanical forces influence the dynamics of growing tissues. Computer simulations are employed to study the importance of interfacial effects in tissue competition. It was speculated previously that mechanical pressure determines the competition, where the determining quantity is the homeostatic pressure - the pressure where division and apoptosis balance; the tissue with the higher homeostatic pressure overwhelms the other. In contrast, we find that a weaker tissue can persist in stable coexistence with a stronger tissue, if adhesion between them is small enough. An analytic continuum description can quantitatively describe the underlying mechanism and reproduce the resulting pressures and cell-number fractions. Furthermore, simulations reveal a variety of coexisting structures, ranging from spherical inclusions to a bicontinuous state