  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.
