A physical model of cell metabolism

Jorge Fernandez-De-Cossio-Diaz,Alexei Vazquez

doi:10.1038/s41598-018-26724-7

Abstract

Cell metabolism is characterized by three fundamental energy demands: to sustain cell maintenance, to trigger aerobic fermentation and to achieve maximum metabolic rate. The transition to aerobic fermentation and the maximum metabolic rate are currently understood based on enzymatic cost constraints. Yet, we are lacking a theory explaining the maintenance energy demand. Here we report a physical model of cell metabolism that explains the origin of these three energy scales. Our key hypothesis is that the maintenance energy demand is rooted on the energy expended by molecular motors to fluidize the cytoplasm and counteract molecular crowding. Using this model and independent parameter estimates we make predictions for the three energy scales that are in quantitative agreement with experimental values. The model also recapitulates the dependencies of cell growth with extracellular osmolarity and temperature. This theory brings together biophysics and cell biology in a tractable model that can be applied to understand key principles of cell metabolism.

Highlights

Background proteins reduce the metabolic capacityAnother important observation is the dependency of the model solution with the volume fraction of background proteins φ0
The later behavior is in agreement with the observed decrease of mitochondria protein mass in yeast[25] and mammalian cells[6] at higher growth rates. Taking all this evidence together we provide an explanation for the three key energy scales of cell metabolism
We have investigated a physical model of cell metabolism where the energy demand of cell maintenance represents the energy expended by molecular motors to counteract the entropic forces associated with molecular crowding

Summary

Results

Provided that the motors persistence parameter p is of the order of 1, the energy demand of cell maintenance predicted from this model (~0.5 mol/L/h, Fig. 4B,I) is in the range of what is observed experimentally (around 0.3 mol ATP/L/h)[3] This is a striking observation given that our estimate is based on microscopic parameters characterizing molecular motors (Methods). The maximum yield solution results in higher volume fractions for the oxidative phosphorylation pathway (Fig. 4E), concomitantly with a higher maintenance energy demand associated with the molecular motors activity (Fig. 4B). As expected, cells with higher content of background proteins are more sensitive to temperature changes and the lines are shifted to lower temperatures and growth rates (Fig. 6B)

Discussion

Methods

Vc ln Φ