Cellular heterogeneity results from indirect effects under metabolic tradeoffs

The emergence and maintenance of multicellularity requires the coexistence of diverse cellular populations displaying cooperative relationships. This enables long-term persistence of cellular consortia, particularly under environmental constraints that challenge cell survival. Toxic environments are known to trigger the formation of multicellular consortia capable of dealing with waste while promoting cell diversity as a way to overcome selection barriers. In this context, recent theoretical studies suggest that an environment containing both resources and toxic waste can promote the emergence of complex, spatially distributed proto-organisms exhibiting division of labour and higher-scale features beyond the cell–cell pairwise interactions. Some previous non-spatial models suggest that the presence of a growth inhibitor can trigger the coexistence of competitive species in an antibiotic-resistance context. In this paper, we further explore this idea using both mathematical and computational models taking the most fundamental features of the proto-organisms model interactions. It is shown that this resource-waste environmental context, in which both species are lethally affected by the toxic waste and metabolic tradeoffs are present, favours the maintenance of diverse populations. A spatial, stochastic extension confirms our basic results. The evolutionary and ecological implications of these results are outlined.