Covariance structure in sizes and numbers shows that membrane-bound organelles grow in a more correlated manner when cellular growth rate is limited

Among the fundamental questions in system cell biology is how the cell coordinates synthesis of its components to grow and self-replicate, in correspondence with its environment. While microscopic responses to cellular growth rate have been well studied at genome-scale, and much progress has been made for prokaryotic cells, we still do not have a quantitative, system-level understanding of how the various layers of biological organizations interact to regulate eukaryotic cellular growth. Here we begin to tackle this challenge by quantifying the relationship between cellular growth and membrane-bound organelles.  We simultaneously visualized six organelles in Saccharomyces cerevisiae via confocal hyperspectral microscopy while changing cellular growth rate by applying nutrient shifts and tuning the activity of nutrient-sensing pathways. The covariance structure in the sizes and numbers of different organelles shows that organelles generally grow in a more correlated manner when the growth rate is limited, while the correlation is less visible when the growth rate is higher. Our results potentially suggest that subcellular construction projects are susceptible to a fundamental speed-accuracy tradeoff that could be common to the replication of complex systems more broadly.