Speaker
Description
Many cellular populations are tightly packed, including microbial colonies and biofilms, or tissues and tumours in multicellular organisms. However, little is known about how ensuing mechanical cell-cell interactions reshape evolutionary dynamics and critical outcomes, such as drug resistance. Here, I will show how growth-induced collective motion inherently suppresses the differential displacements of neighbouring cells required for selection to act. Tracking the evolutionary trajectories of slower-growing clones at the expanding edge of yeast colonies, I will demonstrate that such a mechanical screening of fitness differences allows costly resistant mutants to persist orders of magnitude longer than previously thought. I will then introduce a genetically tailored system of synthetic compensatory mutations to show how resistant lineages can cross substantial fitness valleys and permanently escape selection. Finally, I will expand the discussion to a novel matrix-embedded yeast spheroid model to explore evolutionary dynamics and treatment failure in 3D. The presented results suggests that, in crowded populations, cells cooperate with surrounding neighbours through inevitable mechanical interactions. This effect has to be considered when predicting evolutionary outcomes, including the emergence of resistance in biofilms and cancer, or when refining novel evolution-based treatment strategies, such as adaptive therapy.
