System-scale quantitative measurement recognizes scaling exponents between multiple organelle volumes

A fundamental question in cellular biophysics is how the multiple components of the cell are coordinately built to optimize physiological function. A powerful tool to infer the constraints that a given compartment places on other compartments is to examine how their physical volumes scale with each other: bulk process constraints tend to lead to isometric scaling between volumes, while transport limited relations yield sublinear scaling. However, these simple interpretations of scaling exponents are complicated by the constraint that the components as a whole must simultaneously share the volume of the cell, a constraint whose consequences have been virtually unexplored due to technological limitations to simultaneously imaging multiple compartments at a time. To map out the landscape of inferred constraints in the eukaryotic cell at systems-scale, we extracted volume scaling exponents between every pair of the 6 major metabolic organelles measured simultaneously in the budding yeast Saccharomyces cerevisiae as well as the volume of the cell and an estimate of the volume of the nucleocytoplasm. The exponents revealed a variety of relationships, ranging from 0 (independence) to 3/2 (area-volume relationship). Finally, by examining how these scaling relations change with both the size of the cell as well as their growth rates, we will present our initial work on using these scaling rules to constrain models of cellular resource allocation during cellular growth.