‘Social’ versus ‘asocial’ cells—dynamic competition flux balance analysis

Abstract In multicellular organisms cells compete for resources or growth factors. If any one cell type wins, the co-existence of diverse cell types disappears. Existing dynamic Flux Balance Analysis (dFBA) does not accommodate changes in cell density caused by competition. Therefore we here develop ‘dynamic competition Flux Balance Analysis’ (dcFBA). With total biomass synthesis as objective, lower-growth-yield cells were outcompeted even when cells synthesized mutually required nutrients. Signal transduction between cells established co-existence, which suggests that such ‘socialness’ is required for multicellularity. Whilst mutants with increased specific growth rate did not outgrow the other cell types, loss of social characteristics did enable a mutant to outgrow the other cells. We discuss that ‘asocialness’ rather than enhanced growth rates, i.e., a reduced sensitivity to regulatory factors rather than enhanced growth rates, may characterize cancer cells and organisms causing ecological blooms. Therapies reinforcing cross-regulation may therefore be more effective than those targeting replication rates.