Consequences of context-dependent cellular basal metabolic rate (BMR). (a) Cellular BMR scales as ∝M−¼
in-vivo but mammalian cells cultured in-vitro have the same cellular BMR regardless of the mass of the source organism (∝M0). (a–i) In-vitro cell culture of human cells leads to a cellular BMR ~one order of magnitude larger than that of a normal human25,27. (a–ii) A high-fidelity, physiologically relevant human-on-a-chip (HOC) should be designed with mechanisms to ensure cellular BMR matches typical in-vivo values for the organism to be modeled. (b) Failure to account for the context-dependent behavior of cells can substantially alter the modeled system BMR, especially for larger animals25,28. Graphs reproduced using previously published data and relationships25,28,72.