‘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.

Arsenic Contamination of Groundwater Is Determined by Complex Interactions between Various Chemical and Biological Processes

“…Biodegradation should be linked to growth or detoxification in order to provide a selective advantage to the cells that bear the catalytic activity [ 274 ]. But, unlike the chemical and biochemical aspects where approaches such as flux balance analysis may help, such microbial growth facets of biodegradation are more difficult to implement in a predictive system, although, here, the new “dynamic competition FBA” may help [ 275 ]. Microbial communities contain multiple variants of pan enzyme (corresponding to enzymatic activity without cell borders) [ 270 , 276 ] with non-identical efficiencies [ 277 ].…”

“…Using a second aspect of systems biology, i.e., flux balance analysis [ 268 ], on genome-wide metabolic maps, optimal supply rates of nutrients and the resulting production of metabolites and species of arsenic and iron can be calculated. Recently, a type of FBA that accommodates competition between different cell types for a given influx of substrate has become available [ 275 ], which should also be relevant.…”