title: 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.
authors.affiliation: Centre for Integrative Bioinformatics (IBIVU), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. douwe.molenaar@falw.vu.nl
authors.forename: Douwe
authors.initials: D
authors.lastname: Molenaar
authors.forename: Rogier
authors.initials: R
authors.lastname: van Berlo
authors.forename: Dick
authors.initials: D
authors.lastname: de Ridder
authors.forename: Bas
authors.initials: B
authors.lastname: Teusink
mesh_terms: D000818:Animals; D048708:Cell Growth Processes; D002477:Cells / Q000378:metabolism*; D008954:Models, Biological; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D011994:Recombinant Proteins