Chirality provides a direct fitness advantage and facilitates intermixing in cellular aggregates

Short Abstract Is it better to be left- or right-handed? The answer depends on whether the goal is making a handshake or winning a boxing match. The need for coordination favors the handedness of the majority, but being different could also provide an advantage. The same rules could apply to microbial colonies and cancer tumors. Like humans, cells often have handedness (chirality) that reflects the lack of mirror symmetry in their shapes or movement patterns. We find that cells gain a substantial fitness advantage by either increasing the magnitude of their chirality or switching to the opposite handedness. Selection for specific chirality is mediated by the formation of bulges along the colony edge in regions where cells with different chiralities meet. Long Abstract Chirality in shape and motility can evolve rapidly in microbes and cancer cells. To determine how chirality affects cell fitness, we developed a model of chiral growth in compact aggregates such as microbial colonies and solid tumors. Our model recapitulates previous experimental findings and shows that mutant cells can invade by increasing their chirality or switching their handedness. The invasion results either in a takeover or stable coexistence between the mutant and the ancestor depending on their relative chirality. For large chiralities, the coexistence is accompanied by strong intermixing between the cells, while spatial segregation occurs otherwise. We show that the competition within the aggregate is mediated by bulges in regions where the cells with different chiralities meet. The two-way coupling between aggregate shape and natural selection is described by the chiral Kardar-Parisi-Zhang equation coupled to the Burgers’ equation with multiplicative noise. We solve for the key features of this theory to explain the origin of selection on chirality. Overall, our work suggests that chirality could be an important ecological trait that mediates competition, invasion, and spatial structure in cellular populations.