Shifts in growth strategies reflect tradeoffs in cellular economics

Abstract

The growth rate-dependent regulation of cell size, ribosomal content, and metabolic efficiency follows a common pattern in unicellular organisms: with increasing growth rates, cell size and ribosomal content increase and a shift to energetically inefficient metabolism takes place. The latter two phenomena are also observed in fast growing tumour cells and cell lines. These patterns suggest a fundamental principle of design. In biology such designs can often be understood as the result of the optimization of fitness. Here we show that in basic models of self-replicating systems these patterns are the consequence of maximizing the growth rate. Whereas most models of cellular growth consider a part of physiology, for instance only metabolism, the approach presented here integrates several subsystems to a complete self-replicating system. Such models can yield fundamentally different optimal strategies. In particular, it is shown how the shift in metabolic efficiency originates from a tradeoff between investments in enzyme synthesis and metabolic yields for alternative catabolic pathways. The models elucidate how the optimization of growth by natural selection shapes growth strategies.

Evolving strategies for single-celled organisms in multi-nutrient environments

“…the lag phase or even the strict sequential nature of nutrient uptake. This is confirmed by recent experimental findings that demonstrate this plasticity using artificial wet-lab evolution (Molenaar et al, 2009). For as long as the plasticity of dual nutrient uptake is established, then the details of the implementation are mostly irrelevant.…”

Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol

“…Both mechanisms together produce global changes that reorganize that metabolic network for optimal growth. The use of energy inefficient and wasteful metabolite overflow appears to be an essential trade-off to achieve fast growth under conditions where carbon source is abundant, as suggested by other studies 31,33 . It will be interesting to see how the optimized network of the fast growing mutants described here fares under nutrient-limiting conditions where biosynthetic and efficiency requirements and priorities are different.…”

“…Prior studies have suggested that less efficient overflow metabolism may be advantageous when carbon source is non-limiting and protect against methylglyoxal toxicity 30 . Overflow has also been proposed to represent a trade-off between energy and biomass yield and the biosynthetic costs of respiration that occur during fast growth 31 . In addition, competition for membrane space between substrate uptake and respiration has also been proposed to be a constraint leading to carbon wasting 32 .…”

Poster abstracts of GCB 2015

“…In order to assess the importance of these constraints in predicting cellular growth and reaction rates, we compared nonlinear simulations of a simplified whole-cell metabolic model (based on previous work [MvBdRT09]) to FBA and to FBA with molecular crowding. FBA growth rate predictions are realistic only at low growth rates, while FBA with molecular crowding provides qualitatively acceptable predictions at all growth rates.…”