Contributed Talk

Collective motion attenuates natural selection in crowded cellular populations

Jona Kayser, Carl Schreck, Matti Gralka, Diana Fusco, Oskar Hallatschek

University of California - Berkeley, Physics Department, Stanley Hall, Berkeley, CA 94720, USA

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The successive acquisition of mutations is the primary driver of oncogenesis and cancer progression. Throughout the growth process, arising mutant clones have to compete with ancestral genotypes via natural selection. Yet, for dense cellular assemblies, such as solid tumors, little is known about how these evolutionary forces are shaped by the inherent mechanical cell-cell interactions underlying spatial population expansion. Here, by tracking slower-growing clones in a microbial model system, I show that the collective motion of cells can attenuate selection pressures, preventing costly mutations from being weeded out rapidly. The presented observations can be understood in the framework of an effective surface tension. Using a combination of microbial experiments and computational models I demonstrate that the intrinsic cooperative nature of growth-induced forces suppress the differential displacements required for selection to act. This mechanical screening of fitness differences facilitates the prolonged persistence of costly drug resistant mutations, a primary cause of cancer treatment failure.