‘Social’ versus ‘Asocial’ cells--- Dynamic Competition Flux Balance Analysis

Abstract

Abstract In multicellular organisms, different cell types compete for resources or growth factors, endangering cellular diversity as well as co-existence. To address this, we developed ‘dynamic cell-cell competition FBA’ (dcFBA). With total biomass synthesis as objective, we found that lower-growth-yield cell types face extinction even when they synthesized mutually required metabolic commodities. Signal transduction between cells promoted co-existence, when turning the cells into mutually regulatory and responsive ‘social cells’. Mutants with specific growth rate but intact signal transduction did not outgrow others. However, loss of its social characteristics enabled a mutant to dominate the other cell types with higher specific growth rates and bring those to extinction. A corollary is that cancer arises from reduced sensitivity to regulatory factors rather than enhanced specific growth rates. Therapies reinforcing cells’ cross-regulation, perhaps through alternative signaling routes, may therefore be more effective than those targeting replication rates.