Cooperative nutrient accumulation sustains growth of mammalian cells

The coordination of metabolic processes to allow increased nutrient uptake and utilization for macromolecular synthesis is central for cell growth. Although studies of bulk cell populations have revealed important metabolic and signaling requirements that impact cell growth on long time scales, whether the same regulation influences short-term cell growth remains an open question. Here we investigate cell growth by monitoring mass accumulation of mammalian cells while rapidly depleting particular nutrients. Within minutes following the depletion of glucose or glutamine, we observe a growth reduction that is larger than the mass accumulation rate of the nutrient. This indicates that if one particular nutrient is depleted, the cell rapidly adjusts the amount that other nutrients are accumulated, which is consistent with cooperative nutrient accumulation. Population measurements of nutrient sensing pathways involving mTOR, AKT, ERK, PKA, MST1, or AMPK, or pro-survival pathways involving autophagy suggest that they do not mediate this growth reduction. Furthermore, the protein synthesis rate does not change proportionally to the mass accumulation rate over these time scales, suggesting that intracellular metabolic pools buffer the growth response. Our findings demonstrate that cell growth can be regulated over much shorter time scales than previously appreciated.National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)National Cancer Institute (U.S.). Physical Sciences Oncology Center (U54CA143874)National Institutes of Health (U.S.) (Contract R01GM085457)National Cancer Institute (U.S.) (Fellowship F31CA167872)National Institutes of Health (U.S.) (Interdepartmental Biotechnology Training Program 5T32GM008334